• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.116-116
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• 1997

Complex formation of practically insoluble dexamethasone dipropionate (DDP) with ${\beta}$-cyclodextrin (${\beta}$-CD), dimethyl-${\beta}$-cyclodextrin (DMCD), trimethyl-${\beta}$-cyclodextrin (TMCD), 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD) and sulfobutyl ether ${\beta}$-cyclodextrin (SBCD) in water was investigated by solubility method at various temperatures. Water solubility of DDP was found to be 1.78 $\mu\textrm{g}$/$m\ell$ at 37$^{\circ}C$. Propylene glycol (PG)-water cosolvent increased the solubility of DDP, but the solubilization was not sufficient (8.93 $\mu\textrm{g}$/$m\ell$ in 20% PG). The addition of CD markedly increased the solubility of DDP in water, and A$\sub$L/ type phase solubility diagrams were obtained with ${\beta}$-CD, TMCD, HPCD and SBCD, where the apparent stability constants of the soluble complexes at 25$^{\circ}C$ were determined to be 1388, 216, 1054, and 1992 M$\^$-1/, respectively. However, DMCD remarkably increased the solubility of DDP, and showed an A$\sub$P/ type diagram, suggesting that DMCD forms a soluble complex of high order with DDP. The stability constant for the DDP-DMCD complex at 25$^{\circ}C$ was determined to be 19132 M$\^$-1/. The thermodynamic parameters were calculated for the inclusion complex formation in aqueous solution. CD (1${\times}$10$\^$-2/M) remarkably decreased the partition coefficients of DDP between isopropyl myristate/water in the order of TMCD < ${\beta}$-CD < HPCD < SBCD < DMCD, and in squalane/water system in the order of HPCD < TMCD < ${\beta}$-CD < DMCD < DMCD $\leq$ SBCD. This finding represents that, in a o/w type cream, cyclodextrin complexation with DDP may result in high concentration of DDP in aqueous phase. The permeation of DDP through a cellophane membrane was highly suppressed by the addition of CD, and the degree of suppression was different among CDs, indicating that CD may control the skin permeation of DDP. The dissolution rates of solid dispersions with CDs were much faster than those of drugs alone and corresponding physical mixtures. All DDP-CD solid dispersions exceeded the equilibrium solubility. Consequently these results suggest that complex formation of DDP with CDs may provide useful means to markedly enhance the solubility, and CDs are useful in the semi-solid preparations such as creams and gels for topical application.

• 대한지하수환경학회지
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• 제4권4호
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• pp.199-211
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• 1997

방사성폐기물의 지하심부 처분을 위한 수리지구화학적 기초자료를 얻기 위하여 국내 화강암질암을 대수층으로 하는 지표수 및 지하수를 대상으로 시료채취와 문헌조사를 통하여 dataset을 구축하였다. 심도에 따른 용존물질의 절대 및 상대함량과 거동특성을 통계적으로 파악하고 지하수의 화학적 조성의 원인이 되는 물-암석반응을 열역학적 해석과 결부하여 규명하였다. 화강암질암 대수층에서 총용존물질량은 심도에 따라 통계적으로 유의하게 증가함으로써 심부로 갈수록 물-암석반응을 많이 거친 물이 존재함을 나타낸다. 지하수의 조성은 초기의 $Ca^{2＋}$－(C $l^{－}$＋S $O_4$$^{2－}$ ) 또는 $Ca^{2＋}$-HC $O_3$$^{－}$ 유형에서 시작하여 점차 $Ca^{2＋}$-HC $O_3$$^{－}$ 유형을 거친 후 최종적으로 $Na^{＋}$-HC $O_3$$^{－}$ 또는 $Na^{＋}$－(C $l^{－}$＋S $O_4$$^{2－}$ ) 유형으로 진화하는 경향을 보인다. 이러한 특징은 $Ca^{2＋}$, $Na^{+}$ , $SiO_2$(aq)가 대표하는 다음의 세 가지 기제에 의하여 설명이 가능하다. 1) 천부지하수의 화학조성을 조절하는 가장 주된 반응은 방해석의 용해이나 중간지하수를 거치면서 방해석 포화상태에 이르러 광물상으로 침전되며 심부지하수에서는 $Ca^{2＋}$의 함량이 감소한다. 2) 심부지하수에서는 사장석의 용해가 주도적인 반응으로 작용하며 $Na^{＋}$를 공급하므로써 함량을 증가시킨다. 3) 중간 및 심부지하수에서는 kaolinite-smectite 또는/그리고 kaolinite-illite 간의 반응이 평형에 도달함으로써 용존 $SiO_2$(aq) 함량을 유지시키며 또한 이들 반응은 심부지하수에서 $Mg^{2＋}$ 및 $K^{＋}$가 결핍되는 현상의 중요한 원인이 된다.

• 한국해양학회지:바다
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• 제10권1호
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• pp.56-68
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• 2005

강화도 남단 갯벌의 상부조간대 세 정점에서 퇴적물 시료를 채취하여, 공극수에서 질산염 등 영양염을 분석하였다. 질산염의 공극수내 분포를 단순한 1차원 모델로 분석한 결과, 탈질산화율은 장화리에서 $7.8{\sim}9.4{\times}10^{-7}{\mu}mol{\cdot}cm^{-2}{\cdot}sec^{-1}$, 동막에서 $1.4{\sim}3.6{\times}10^{-7}{\mu}mol{\cdot}cm^{-2}{\cdot}sec^{-1}$로 추정되었다. 이는 타 지역에서 보고된 반응속도와 별 차이가 나지 않는 규모였다. 탈질산화율은 여름철에 낮았으며, 퇴적물 입도가 상대적으로 조립한 장소에서 1.5배 이상 빠르게 나타나서, 입도가 탈질산화 반응물질의 공급속도를 조절하는 중요한 인자 중의 하나로 판단되었다. 탈질산화는 무기질소 성분을 $N_2$로 영구적으로 갯벌의 계 외로 제거함으로써 지화학적 정화능으로 제시될 수 있지만, 열역학적 판단기준으로 보면 계에 대해 정화라는 개념을 부여하는 데에는 문제가 있다고 판단된다. 또한 현재 갯벌이란 용어가 생태환경적 기능이 상이한 염습지, 모래갯벌과 펄갯벌을 통칭하고 있어서 과학적인 분류가 시급한 것으로 나타났다.

• Macromolecular Research
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• 제13권3호
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• pp.167-175
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• 2005

This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4773-4780
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• 2014

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

• 한국수산과학회지
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• 제18권5호
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• pp.455-463
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• 1985

말쥐치 육의 근원섬유단백질을 추출하고 몇가지 온도조건이 그 변성에 미치는 영향을 실험하였으며, sucrose와 sorbitol 및 아미노산을 첨가하였을 때의 변성억제효과에 관하여도 비교 검토하였다. 실험에서 얻은 결과를 요약하면 다음과 같다. 1. 말쥐치 근원섬유단백질의 $25^{\circ}C,\;30^{\circ}C,\;35^{\circ}C$에서의 변성속도정수($K_D$값)는 각각 $19.52{\times}10^{-5},\;112.25{\times}10^{-5},\;247.20{\times}10^{-5}$이었다. 활성화 에너지${\Delta}E$값은 43 kcal/mole, 활성화엔탈피 ${\Delta}H$는 42.4kcal/mole, 활성화 엔트로피 ${\Delta}S$는 66.79 e.u., 그리고 자유에너지 ${\Delta}G$는 22.4kcal/mole이었다. 2. 말쥐치 근원섬유단백질이 $0^{\circ}C$에서 96시간 경과했을 때는 최초 활성의 $53\%$가 감소하였고, $-20^{\circ}C$에서 60시간이 경과했을 때는 약 $72\%$가 감소했다. 3. 농도별 첨가제의 가열변성에 대한 억제 효과는 1M Na-Glu>1M sorbitol>1.25M Gly>0.5M sucrose>1.25M Ala의 순이며, 변성억제효과 값 ${\Delta}E$는 Na-Glu가 1.25, sorbitol이 0.58, Gly이 0.28, sucrose가 0.21, Ala이 0.05이였다. 4. 혼성 첨가시는 1M Na-Glu+1.25M Gly>1M sorbitol+1.25 M Gly>1M sorbito1+0.5M sucrose>1M sorbito1+1M Na-Glu순으로 가열변성억제효과를 가지고 있으며, 이들의 $K_D$값은 위의 순서대로 $25^{\circ}C$에서 각각 $1.38{\times}10^{-5},\;11.75{\times}10^{-5},\;14.95{\times}10^{-5},\;15.66{\times}10^{-5}$으로서 무첨가시보다 $7{\sim}l.2$배의 효과를 나타내고 있었다. 5. 혼성 첨가시의 열역학적 함수로서 활성화 에너지, 활성화 엔탈피, 활성화 엔트로피, 자유 에너지는 Na-Glu+Gly 일 때, 68.4kcal/mole, 67.8 kcal/mole, 146.70 e. u., 24kca1/mole이며, sorbitol+Gly은 44kcal/mole, 43.4kcal/mole, 69.14 e. u., 22.8kcal/mole, sorbitol+sucrose는 42.7kcal/mole, 42.1kcal/mole 65.26 e. u., 22.6kcal/mole이고. sorbitol+Na-Glu는 49kcal/mole, 48.4kcal/mole, 86.49 e. u., 22.6kcal/mole이었다. 6. 냉동중의 변성억제효과는 1M Na-Glu+1.25M Gly/1M sorbito1+0.5M sucrose>1M sorbitol+1.25M $Gly{\sim}lM$ sorbito1+1M Na-Glu의 순으로 좋았다.

• 농약과학회지
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• 제2권1호
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• pp.46-52
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• 1998

[ $45^{\circ}C$ ]의 15%(v/v) dioxane 수용액중에서 살충성 buprofezin(IUPAC : tert-butylimino-3-iso-propyl-5-phenylperhydro-1,3,5-thiadiazin-4-one)의 가수분해 반응속도상수와 pka상수(5.60)를 측정하고 pH-효과, 용매효과(m=0.34, n=2.45 및 $1{\gg}m$), 열역학적 활성화 파라미터(pH 4.0, ${\Delta}H^{\neq}$= 11.12 $kcal{\cdot}mol^{-1}$, ${\Delta}S^{\neq}$=-5.0e.u. 및 $E_{act.}$=11.76Kcal), 반응 속도식등의 반응 속도론적 및 생성물분석(1-isopropyl-3-phenyl urea) 등의 비속도론적 실험결과를 얻었다. 이들 자료의 검토로부터 pH 8.0이하의 산성용액에서는 특정($k_{H3O+}$)및 일반 산-촉매반응에 의한 $A-S_{E}2$형 및 A-2(또는 $A_{AC}2$)형 반응, 그리고 pH 9.0이상의 알카리성 용액에서는 일반염기 촉매반응($k_{H2O}$)에 의한 친핵성 첨가-제거 ($Ad_{N}-E$) 반응이 사면체($sp^{3}$) 중간체를 경유하는 궤도-조절 반응으로 진행되는 일련의 가수분해 반응메카니즘을 제안하였다. 또한, Buprofezin은 산성(pH8.0이하)용액보다 염기성(pH8.0이상) 용액중($k=10^{-8}sec.^{-1}$)에서 더욱 안정하였으며 $45^{\circ}C$의 중성(pH 7.0) 수용액 중에서 반감기($t=\frac{1}{2}$)는 약 3개월이었다.