• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.93-102
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• 1996

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as nephrotoxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and broadening the clinical spectrum of activity of cisplatin. We synthesized new Pt(II) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,3-bis(diphenyl phosphino)propane (DPPP) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of PC-1 [Pt(cis-dach) (DPPP)]. $2NO_3_2$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC-1 was demonstrated acceptable antitumor activity aganist SKOV -3, OVCAR-3 human ovarian adenocarcinomacells and significant activity as compared with that of cisplatin. The toxicity of PC-1 was found quite less than that of cisplatin using MTT, $[^3H]thymidine$ uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Bulletin of the Korean Chemical Society
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• v.34 no.7
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• pp.2016-2022
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• 2013

Ionically modified ${\beta}$-cyclodextrins, which have excellent water-solubility, have been interested in purification technology as well as drug carrier system. The present study summarizes the synthesis and characterization of cationic and anionic ${\beta}$-cyclodextrin (${\beta}$-CyD) products using by polycondensation. The oligo (${\beta}$-CyD)s are synthesized from ${\beta}$-CyD, epichlorohydrin (EP) and choline chloride (CC; for cationic polymer) or chloroacetic acid (CAA; for anionic polymer) through one step polycondenstaion process. Unlike the previous studies, we successfully purified the ionic ${\beta}$-CyD condensation products from the ${\beta}$-CyD reaction mixtures and accomplished a great level of structural analysis. The detailed structural analysis of these ionic ${\beta}$-CyD compounds is done by $^1H$ NMR, MALDI-TOF as well as GPC analysis and confirms the formation of oligomers with a few units of ${\beta}$-CyD. We found that the sequence of reactant addition also could effect on the molecular weight of the resulting product as well as the molar ratio of the reactants. Finally, we used the cationic and anionic ${\beta}$-CyD oligomers for fabricating multilayer films by layer-layer process.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.541-543
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• 2005

Recently many efforts have been made to develop new therapeutic agents against skin pigmentation abnormalities. The aim of this study is to investigate the skin-whitening effect of Gleditsia Sinensis Lam and to develop new drug delivery carrier. Inhibitory effaces of Gleditsia Sinensis Lam extracts on melanin synthesis were studied. Namely, UV-absorbing ability, free radical scavenging activity and tyrosinase inhibitory of Gleditsia Sinensis Lam extracts were investigated As a result, the extracts of Gleditsia Sinensis Lam were found to inhibit the activity of tyrosinase. Moreover they absorbed wavelength in the UV-B and UV-C region, and extracts of Gleditsia Sinensis Lam had free radical scavenging activity. In this study, in order to administer these ingredient effectively, the shape of liposome observed by TEM was spherical and uniform.

• Asian Oncology Nursing
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• v.12 no.2
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• pp.147-155
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• 2012

Purpose: The purpose of this study was to compare and check the levels of cancer pain management knowledge and awareness between doctors and nurses in a tertiary hospital and to develop an intervention program. Methods: Participants were 725 nurses and 95 doctors working in a hospital from May 2 to 29, 2009. Data were analyzed using t-tests, ${\chi}^2$-tests, and ANOVA with SPSS WIN 18.0. Results: In a comparison of the pain management score, nurses showed significant results for age (p<.001), carrier (p<.001), education (p<.001), workplace (p<.001), and doctors showed significant results only for age (p=.032). Doctors' marks were significantly higher than nurses' in pain management scores (p<.001). Knowledge about analgesic medication (t=-5.38, p<.001) and analgesic drug effect (t=-8.59, p<.001) were significantly different in the pain management subcategory score between nurses and doctors. There were four items with different awareness levels related to analgesics between nurses and doctors. Conclusion: The findings of this study demonstrate that it is possible to develop pain education content for nurses and doctors. The findings of this study are useful when seeking to change the awareness level of a medical team regarding opioid analgesics.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.295-300
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• 2011

Paclitaxel is a well known anticancer agent and has been a pharmaceutical challenge because of its extremely poor water-solubility and susceptibility to the p-glycoprotein (p-gp)-mediated efflux in multi-drug resistant (MDR) cancer cells. Tributyrin (TB), a triglyceride with relatively short fatty acid chains, was chosen as solubilizing vehicle for paclitaxel based on the solubility study (26.6 mg/mL). Tributyrin (10%) o/w emulsion containing paclitaxel (5%), egg phosphatidylcholine (5%) and pegylated phospholipid (0.5%) was prepared by high pressure homogenization to obtain submicron-sized emulsion. The mean particle size of the resultant TB emulsion was 395.5 nm. Paclitaxel in TB emulsion showed higher anticancer activity against human breast cancer cell line, MCF-7, than free form delivered in DMSO solution. On the other hand, its anticancer activity was significantly reduced in MCF-7/ADR, a MDR variant cancer cell line of MCF-7, and recovered by the presence of verapamil, suggesting of the susceptibility to the p-gp mediated efflux even though paclitaxel was encapsulated into emulsion. The TB emulsion showed great potential as a promising vehicle for water-insoluble anticancer agent, paclitaxel.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.1-9
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• 2009

As many new drug substances contained various aromatic rings and fluorine attached to an electron rich aromatic ring or on the meta-position, a strategy towards improvement in aromatic fluorination of these compounds is highly desirable. The introduction of fluorine-18 onto aromatic rings showed in the limited condition containing electron withdrawing group (EWG) on the para- or ortho-position to get reasonable radiochemical yield so far. No-carrier added (NCA) [$^{18}F$]fluoroarene syntheses by iodonium salts recently reported that has the potential to greatly increase the yield in systems or positions that normally not reactive enough to give sufficient yields in simple model reaction. This review describes the methodological approach towards effective aromatic fluorination by diaryliodonium salts and future prospects in an application of novel PET radiotracer.

• Parasites, Hosts and Diseases
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• v.44 no.1 s.137
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• pp.55-61
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• 2006

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with $5{\time}10^3$ metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was started and continued for 12 days. Thalidomide was orally administrated 30 mg/kg/day and glucantime was administrated intraperitoneally (200 mg/kg/day). It was shown that the combined therapy is more effective than single therapies with each one of the drugs since the foot pad swelling in the group of mice received thalidomide and glucantime was significantly decreased (0.9 :t 0.2 mm) compared to mice treated with either glucantime, thalidomide, or carrier alone (1.2 :t 0.25, 1.4 :t 0.3, and 1.7 :t 0.27 mm, respectively). Cytokine study showed that the effect of thalidomide was not dependent on IL-12; however, it up-regulated IFN-yand down-regulated IL-10 production. Conclusively, thalidomide seems promising as a conjunctive therapy with antimony in murine model of visceral leishmaniasis.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.162-168
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• 2011

Many ligands have been experimentally designed and tested for their activities as inhibitors against bacterial enoyl-ACP reductase (FabI), ENR. Here the binding energies of the reported ligands with the E. coli ENR-$NAD^+$ were calculated, analyzed and compared, and their molecular dynamics (MD) simulation study was performed. IDN, ZAM and AYM ligands were calculated to have larger binding energies than TCL and IDN has the largest binding energy among the considered ligands (TCL, S54, E26, ZAM, AYM and IDN). The contribution of residues to the ligand binding energy is larger in E. coli ENR-NAD+-IDN than in E. coli ENR-$NAD^+$-TCL, while the contribution of $NAD^+$ is smaller for IDN than for TCL. The large-size ligands having considerable interactions with residues and $NAD^+$ have many effective functional groups such as aromatic $\pi$ rings, acidic hydroxyl groups, and polarizable amide carbonyl groups in common. The cation-$\pi$ interactions have large binding energies, positively charged residues strongly interact with polarisable amide carbonyl group, and the acidic phenoxyl group has strong H-bond interactions. The residues which have strong interactions with the ligands in common are Y146, Y156, M159 and K163. This study of the reported inhibitor candidates is expected to assist the design of feasible ENR inhibitors.

• Archives of Pharmacal Research
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• v.2 no.1
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• pp.49-64
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• 1979

In an atempt to elucidate further physicochemical properties of furosemide-PVP coprecipitates, extensive investigations such as TLC, UV,IR, NMR, X-ray diffraction, TGA and DTA studies were carried out for the furosemide test systems. X-ray diffraction studies revealed that the pure furosemide and the furosemide contained within a physical mixture were crystalline in nature. However, there was no crystallinity evident in the 1:5 furosemide-PVP 40,000 coprecipitate system, even after standing for two years. The various ratio furosemide-PVP 40,000 coprecipitate systems revealed that the coprecipitate containing a greater amount of PVP 40,000 than that of furosemide showed a crystalline state of furosemide and that the minimum amounts of PVP to make amorphous form of furosemide was 1:1 ratio of furosemide to PVP. From the furosemide-PVP coprecipitate systems with PVP of different molecular weights of 10,000, 40,000 and 360,000, all the 1:1 ratio coprecipitates did not exhibit any crystallinity of furosemide, whereas all the 2:1 ratio coprecipitates showed a presence of crystalline furosemide. All the coprecipitated preparations with PEG 4,000 and with PEG 6,000 showed the diffraction peaks indicating the presence of crystalline furosemide. The comparison of infrared spectra of the physical mixture and the coprecipitate showed an interaction such as association between the functional groups of furosemide and PVP in the molecular level, whereas the studies by TLC, UV and NMR showed its dissociation in methanol solution. The weight losses in TGA curves showed all the same patterns. However, a little different transition form in DTA thermograms was shown between the physical mixture and the coprecipitate, indicating the different thermal property.

• Macromolecular Research
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• v.13 no.4
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• pp.344-351
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• 2005

pH-sensitive block copolymers were synthesized by coupling reaction of sulfamethazine and amphiphilic diblock copolymer, and their micellization-demicellization behavior was investigated. Sulfamethazine (SM), a derivative of sulfonamide, was introduced as a pH responsive moiety while methoxy poly(ethylene glycol)poly(D,L-lactide) (MPEG-PDLLA) and methoxy poly(ethylene glycol)-poly($D,L-lactide-co-{\varepsilon}-caprolactone$) (MPEG-PCLA) were used as biodegradable amphiphilic diblock copolymers. After the sulfamethazine was carboxylated by the reaction with succinic anhydride, the diblock copolymer was conjugated with sulfamethazine by coupling reaction in the presence of DCC. The critical micelle concentration (CMC) and mean diameter of the micelles were examined at various pH conditions through fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. For MPEG-PDLLA-SM and MPEG-PCLA-SM solutions, the pH-dependent micellization-demicellization was achieved within a narrow pH band, which was not observed in the MPEG-PDLLA and MPEG-PCLA solutions. The micelle showed a spherical morphology and had a very narrow size distribution. This pH-sensitive block copolymer shows potential as a site-targeted drug carrier.