• Title/Summary/Keyword: impurity control

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Solid-Phase Refolding Technology in Recombinant Proteins Recovery: Application Examples to Various Biopharmaceutical Proteins (유전자재조합 단백질 회수 공정에서의 고체상 재접힘 기술: 여러 바이오의약 단백질에의 적용 사례)

  • Kim, Min Young;Suh, Chang Woo;Kim, Chang Sung;Jo, Tae Hoon;Park, Sang Joong;Choi, Won Chan;Lee, Eun Kyu
    • Korean Chemical Engineering Research
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    • v.43 no.2
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    • pp.187-201
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    • 2005
  • Bioprocessing technologies utilizing 'biorecognition' between a solid matrix and a protein is being widely experimented as a means to replacing the conventional, solution-based technology. Frequently the matrices are chromatographic resins with specific functional groups exposed outside. Since the reactions of and interactions with the proteins occur as they are attached to the solid matrix, this 'solid-phase' processing has distinct advantages over the solution-phase technology. Solid-phase refolding of inclusion body proteins uses ion exchange resins to adsorb denaturant-dissolved inclusion body. As the denaturant is slowly removed from the micromoiety around the protein, it is refolded into a native, three-dimensional structure. Once the refolding is complete, the folded protein can be eluted by a conventional elution technique such as the salt-gradient. This concept was successfully extended to 'EBA (expanded bed adsorption)-mediated refolding,' in which the denaturant-dissolved inclusion body in whole cell homogenate is adsorbed to a Streamline resin while cell debris and other impurity proteins are removed by the EBA action. The adsorbed protein follows the same refolding steps. This solid-phase refolding process shows the potential to improve the refolding yield, reduce the number of processing steps and the processing volume and time, and thus improve the overall process economics significantly. In this paper, the experimental results of the solid-phase refolding technology applied to several biopharmaceutical proteins of various types are presented.

Beneficiation of Low Grade Sericite Using Attrition Scrubbing and Sedimentation (해쇄 및 침강분리에 의한 저품위 견운모의 품위향상 특성)

  • Chae, Sungki;Kim, Hyunsoo;Kim, Sangbae;Kim, Wantae
    • Journal of the Mineralogical Society of Korea
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    • v.30 no.4
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    • pp.137-147
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    • 2017
  • Sericite is a clay mineral that has a wide applications in the industry, depending on its purity. To maintain sericite's purity as high as possible it is necessary to remove its gangue minerals or control their contents prior to use for high value-added products and applications. In this study, the wet beneficiation of sericite by applying selective grinding and sedimentation techniques, were investigated. The ore mineral was composed mainly of sericite, quartz and calcite. Analysis showed that the content of sericite increased along with the particle size decrease, but the contents of impurity minerals as quartz and calcite were tended to decrease relatively with particle size decrease. The results of liberation tests using an attrition scrubber showed that the increase in residence time and slurry density have increased the generation of fine particles in -325 mesh size range. It was observed, however, that the contents of impurities such as quartz and calcite in such fine particles also increased during prolonged scrubbing. In the dispersed form without breaking, the yield of the recovered concentrate was 15.4 wt% and the $K_2O$ content was 9.84 wt%, after the dispersed slurry was allowed to settle for 20 minutes. On the other hand, the concentrate yield was increased to 23.4 wt% after 10 minute attrition scrubbing and 40 minute sedimentation, while its $K_2O$ content was decreased to 9.71 wt%. Most of final products were observed as platelet-shaped particles containing Si, Al and K which are main component of sericite.

Thermoelectric Properties of the Reaction Sintered n-type β-SiC (반응소결법으로 제조한 n형 β-SiC의 열전특성)

  • Pai, Chul-Hoon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.3
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    • pp.29-34
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    • 2019
  • Silicon carbide is considered to be a potentially useful material for high-temperature electronic devices, as its large energy band gap and the p-type and/or n-type conduction can be controlled by impurity doping. Particularly, electric conductivity of porous n-type SiC semiconductors fabricated from ${\beta}-SiC$ powder at $2000^{\circ}C$ in $N_2$ atmosphere was comparable to or even larger than the reported values of SiC single crystals in the temperature region of $800^{\circ}C$ to $1000^{\circ}C$, while thermal conductivity was kept as low as 1/10 to 1/30 of that for a dense SiC ceramics. In this work, for the purpose of decreasing sintering temperature, it was attempted to fabricate porous reaction-sintered bodies at low temperatures ($1400-1600^{\circ}C$) by thermal decomposition of polycarbosilane (PCS) impregnated in n-type ${\beta}-SiC$ powder. The repetition of the impregnation and sintering process ($N_2$ atmosphere, $1600^{\circ}C$, 3h) resulted in only a slight increase in the relative density but in a great improvement in the Seebeck coefficient and electrical conductivity. However the power factor which reflects the thermoelectric conversion efficiency of the present work is 1 to 2 orders of magnitude lower than that of the porous SiC semiconductors fabricated by conventional sintering at high temperature, it can be stated that thermoelectric properties of SiC semiconductors fabricated by the present reaction-sintering process could be further improved by precise control of microstructure and carrier density.

The Evaluation of Usefulness of 99Mo-99mTc Generator Using(n,γ)99Mo Developed by Korea Atomic Energy Research ((n,γ)99Mo를 이용한 99Mo-99mTc발생기의 유용성 평가)

  • Seo, Han Kyung;Kim, Jeong Ho;Shim, Cheol Min;Kim, Byung Cheol;Choi, Do Cheol;Gwon, Yong Ju;Park, Yung Sun;Kim, Dong Yun
    • The Korean Journal of Nuclear Medicine Technology
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    • v.17 no.2
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    • pp.48-52
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    • 2013
  • Purpose: The Molybdenum which is the raw material of $^{99}Mo-^{99m}Tc$ generator is produced from the nuclear reactor. However, output has dwindled as the two nuclear reactors supplying the bulk of radioactive material-one in Chalk River, Ontario and the other in Petten, the Netherlands-have been closed for repairs or maintenance. This resulted in the enhancement of its price. So $^{99}Mo-^{99m}Tc$ generator using$(n,{\gamma})^{99}Mo$ is developed by Korea Atomic Energy Research Institute (KAERI). Medicinal availability of this generator is evaluated in this study. Materials and Methods: The radioactivity of $^{99m}Tc$ eluted in generator 1, 2 and 3 unit developed by KAERI was measured. The quality control test of generator such as appearance test, pH test, LAL test, sterility test, chemical impurity (Al) test and radiochemical purity test were performed. Planar and SPECT/CT image sof SD rat (6 weeks, Female) at 2 hr after injection of $^{99m}Tc-HDP$ (hydroxymethylenediphosphonate) (TechneScan HDP, Malinckrodt Medical, Dutch) and $^{99m}Tc-DPD$ (diphosphono-1, 2-propanedicarboxylicacid) (TECEOS, CIS bio international, France) which were labeled with $^{99m}Tc$ eluted in KAERI and commercial generator (40.5 GBq, Malinckrodt Medical, Dutch) using SPECT/CT camera (Symbia, Siemense, Germany) were obtained respectively. Results: The mean radioactivity of $^{99m}Tc$ elution generator 1unit was 4.18 GBq (113 mCi), generator 2 unit was 4.73 GBq (128 mCi) and generator 3 unit was 3.33 GBq (90 mCi). All quality control tests were within normal limit except pyrogentest. Pyrogen test was positive. Planar and SPECT/CT images of rat injected $^{99m}Tc-HDP$ which was labeled with $^{99m}Tc$ eluted in commercial generator show increased uptake in bone, stomach and bowl. Planar images show increased uptake in liver and bone in case of $^{99m}Tc-DPD$. However, images of rat injected $^{99m}Tc-HDP$ and $^{99m}Tc-DPD$ which were labelled $^{99m}Tc$ eluted in KAERI generator show increased uptake in bone, liver and spleen. Conclusion: If shortcoming is removed such as pyrogen and liver appearance, domestic role as an alternative generator is thought to be able to fill and to secure the national medical service by supplying $^{99m}Tc$ when the supply of $^{99m}Tc$ be comes short.

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Effects of Paper Sludge Application on the Chemical Properties of Paddy Soil and Growth of Paddy Rice II. Effects of Paper Sludge Application on the Seasonal Variations of Humus in Paddy Soil (제지(製紙)슬러지의 시용(施用)이 논 토양(土壤)의 화학성(化學性)과 수도생육(水稻生育)에 미치는 영향(影響) II. 토양중(土壤中) 부식형태(腐植形態)에 미치는 슬러지의 영향(影響))

  • Heo, Jong-Soo;Kim, Kwang-Sik
    • Korean Journal of Environmental Agriculture
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    • v.5 no.1
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    • pp.1-10
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    • 1986
  • To investigate the effects of paper sludge on the seasonal variations of soil humus, paper sludges were applied to the pots at the rates of 600㎏/10a which was either preadjusted C/N ratio to 30 : 1 or not adjusted. The effects were compared with those of control. 1) The contents of ether soluble materials, resins, water soluble polysaccharides, hemicellulose, cellulose, ligno-protein, humic acid and fulvic acid were higher in the sludge treated soil than in the control, furthermore, the content of ligno-protein had positive correlation with that of organic nitrogen in soil. 2) Optical density of UV and visible spectra of humic acid obtained from all the treated soil was decreased with increasing wavelength. In functional groups of humic acid, phenolic-OH/alcoholic-OH ratio was slightly higher in the sludge treated soil than in the control. The types of humic acid in all treated soil were P and Rp types. 3) The infrared spectra of humic acid extracted from the soil were characterized by main absorption bands in the regions of $3, 400cm^{-1}$(H-bonded OH), $2,900cm^{-1}$ (aliphatic C-H stretching), $1,630cm^{-1}$ (aromatic C=C and/or H-bonded C=O) and $1,050cm^{-1}$ (Si-O of silicate impurity).

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Radiolysis Assessment of $^{18}F$-FDG According to Automatic Synthesis Module (자동합성장치에 따른 $^{18}F$-FDG의 방사선분해 평가)

  • Kim, Si-Hwal;Kim, Dong-Il;Chi, Yong-Gi;Choi, Sung-Wook;Choi, Choon-Ki;Seok, Jae-Dong
    • The Korean Journal of Nuclear Medicine Technology
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    • v.16 no.1
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    • pp.8-11
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    • 2012
  • Purpose : Among quality control items, the radiochemical impurity must be below 10% of total radioactivity. In this regard, as the recently commercialized automatic synthesis module produces a large amount of 18F-FDG, radiolysis of radiopharmaceuticals is very likely to occur. Thus, this study compared the changes in radiochemical purity regarding radiolysis of $^{18}F$-FDG according to automatic synthesis module. Materials and methods : Cyclotron (PETtrace, GE Healthcare) was used to produce $^{18}F$ and automatic synthesis module (FASTlab, Tracerlab MX, GE Healthcare) was used to achieve synthesis into FDG. For radiochemical purity, Radio-TLC Scanner (AR 2000, Bioscan), GC (Gas Chromatograph, Agilent 7890A) was used to measure the content of ethanol included in $^{18}F$-FDG. Glass board applied with silica gel ($1{\times}10cm$) was used for stationary phase while a mixed liquid formed of acetonitrile and water (ratio 19:1) was used for mobile phase. High-concentration and low-concentration $^{18}F$-FDG were produced in each synthesis module and the radiochemical purity was measured every 2 hours. Results : The purity in low-concentration (below 2.59 GBq/mL) was measured as 99.26%, 98.69%, 98.25%, 98.09% in Tracerlab MX and as 99.09%, 97.83%, 96.89%, 96.62% in FASTlab according to 0, 2, 4, 6 hours changes, respectively. The purity in high-concentration (above 3.7 GBq/mL) was measured as 99.54%, 96.08%, 93.77%, 92.54% in Tracerlab MX and as 99.53%, 95.65%, 92.39%, 89.82% in FASTlab according to 0, 2, 4, 6 hours changes, respectively. Also, ethanol was not detected in GC of $^{18}F$-FDG produced in FASTlab, while 100~300 ppm ethanol was detected in Tracerlab MX. Conclusion : Whereas the change of radiochemical purity was only 3% in low-concentration $^{18}F$-FDG, the change was rapidly increased to 10% in high-concentration. Also, higher radiolysis were observed in $^{18}F$-FDG produced in FASTlab than Tracerlab MX. This is because ethanol is included in the synthesis stage of Tracerlab MX but not in the synthesis stage of FASTlab. Thus, radiolysis is influenced by radioactivity concentration than the inclusion of ethanol, which is the radioprotector. Therefore, after producing high-concentration $^{18}F$-FDG, the content must be diluted through saline to lower concentration.

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The Evaluation of Usefulness of Two Times Elution a Day of $^{99m}Tc$ Using $^{99}Mo$-$^{99m}Tc$ Generator ($^{99m}Tc$ 발생기의 24시간 내 2회 용출의 유용성 평가)

  • Kim, Jeong-Ho;Seo, Han-Kyung;Jeong, Yeong-Hwan;Kim, Yeong-Su;Kim, Byung-Cheol;Gwon, Yong-Ju;Lee, Jeong-Ok;Park, Yeong-Sun;Kim, Dong-Yun
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.2
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    • pp.83-86
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    • 2010
  • Purpose: The Molybdenum which is the raw material of $^{99}Mo$-$^{99m}Tc$ generator (generator) is produced from the nuclear reactor. However, output has dwindled as the two nuclear reactors supplying the bulk of radioactive material-one in Chalk River, Ontario and the other in Petten, the Netherlands-have been closed for repairs or maintenance. This resulted in the enhancement of its price. Therefore we have tried to seek the new method which could run generator to increase activity of $^{99m}Tc$ in this study. Materials and Methods: The $^{99m}Tc$ activity obtained from 5 times elution for 5 days from Monday to Friday using two generators was compared with 10 times elution. Appearance test, pH test, LAL test, sterility test, chemical impurity(Al) test, radio chemical purity test, ratio of $^{99}Mo$/$^{99m}Tc$ activity test have been done to check the stability of $^{99m}Tc$ eluting from generator respectively. Results: The $^{99m}Tc$ activity obtained from 5 times elution for 5 days was 168.2 GBq (4545 mCi) and 10 times was 230.5 GBq (6230 mCi). All quality control tests were within normal limit. Conclusion: We got to know that 2 times elution a day obtained more $^{99m}Tc$ activity than one time elution in this study.

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Analysis of Heavy Metals in $[^{201}Tl]$TICI Injection Using Polarography (폴라로그래피를 이용한 $[^{201}Tl]$염화탈륨 주사액의 중금속 분석)

  • Chun, Kwon-Soo;Suh, Yong-Sup;Yang, Seung-Dae;Ahn, Soon-Hyuk;Kim, Sang-Wook;Choi, Kang-Hyuk;Lee, Dong-Hoon;Lim, Sang-Moo;Yu, Kook-Hyun
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.4
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    • pp.336-343
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    • 2000
  • Purpose: Thallous-201 chloride produced at Korea Cancer Center Hospital(KCCH) is used in detecting cardiovascular disease and cancer. Thallium impurity can cause emesis, catharsis and nausea, so the presence of thallium and other metal impurities should be determined. According to USP and KP, their amounts must be less than 2 ppm in thallium and 5 ppm in total. In this study, the detection method of trace amounts of metal impurities in $[^{201}Tl]$TICI injection with polarography was optimized without environmental contamination. Materials and Methods: For the detection of metal impurities, Osteryoung Square Wave Stripping Voltammetry method was used in Bio-Analytical System (BAS) 50W polarograph. The voltammetry was composed of Dropping Mercury Electrode (DME) as a working electrode, Ag/AgCl as a reference electrode and Pt wire as a counter electrode. Square wave stripping method, which makes use of formation and deformation of amalgam, was adopted to determine the metal impurities, and pH 7 phosphate buffer was used as supporting electrolyte. Results: Tl, Cu and Pb in thallous-201 chloride solution were detected by scanning from 300 mV to -800 mV Calibration curves were made by using $TINO_3,\;CuSO_4\;and\;Pb(NO_3){_2}$ as standard solutions. Tl was confirmed at -450 mV peak potential and Cu at -50 mV Less than 2 ppm of Tl and Cu was detected and Pb was not detected in KCCH-produced thallous-201 chloride injection. Conclusion: Detection limit of thallium and copper is approximately 50 ppb with this method. As a result of this experiment, thallium and other metal impurities in thallous-201 chloride injection, produced at Korea Cancer Center Hospital, are in the regulation of USP and KP Polarograph could be applied for the determination of metal impurities in the quality control of radiopharmaceuticals conveniently without environmental contamination.

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