• KSBB Journal
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• v.16 no.3
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• pp.253-258
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• 2001

Recently, there were many studies not only to enhance drug delivery effect but to reduce side effect. Drug delivery system(DDS) is able to improve efficiency with decreasing side effect of drug dosage. Among these application fields, DDS is often used as the method of drug dosage into the epidermic skin. We investigated characters of transdermal therapeutic system(TTS) and the skin permeability of that with applying DDS. We investigated the permeation of xanthan gum containing drug in rat skin using borizontal membrane cell model. Permeation properties of materials were investigated for water-soluble drug with oxiniacic acid and also for lipophilic drug with clofibrate. The permeation rate of lipophilic drug was found to be faster than that of water-soluble drug in vitro. The rate differences of both water-soluble drug and lipophilic drug according to drug content were negligible. We used glycerin, PEG 600 and oleic acid as enhancers. These results showed that skin permeation rate of each drug across the composite was mainly dependent on the property of base and chemical property of drug etc.. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate. This result suggests a possible use of natural polymer base as a transdermal delivery system of antihyperlipoproteinemic agent.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.440-451
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• 1997

This study was designed to prospect the $^{111}In$-labelled paclitaxel as tumor imaging agent. In order to provide a taxol molecule with a functional group which is able to chelate In-111, taxol-DTPA conjugate and 2'-hemisuccinyltaxol were synthesized by esterification of taxol at C-2'on C-13 carbon with DTPA anhydride and succinic anhydride, respectively. Synthesis yield of the taxol derivatives was 34% for taxol-DTPA and 80% for 2'-hemisuccinyltaxol. Cytotoxicity of the taxol derivatives were measured by MTT method toward cell lines HT29, B16, P388, and CT26. The cytotoxic activities of the taxol derivatives were maintained, although less active than taxol. Radiolabelling of the taxol derivatives were proceeded directly with $^{111}InCl_3$ or indirectly with $^{111}In$-citrate(ligand-exchange method). The ligand-exchange method was not suitable because some precipitates appeared during the reaction. On the contrary, by direct radiolabelling method, we were able to obtain taxol-DTPA-$^{111}In$ in 100% radiochemical yield. However, 2'-hemisuccinyltaxol was not labelled by both methods. Yield and radiochemical purity of the radiolabelled com-pound were determined by HPLC, paper chromatography and instant thin layer chromatography. Taxol-DTPA-$^{111}In$ was characterized to be hydrophilic by lipophilicity test, and nearly non-adhesive to HT29, B16, P388, and CT26 by cell binding affinity test. Binding affinity of the taxol-DTPA-$^{111}In$ complex to serum proteins was also examined by protein precipitation with 30% trichloroacetic acid. The results showed that 30% of the taxol-DTPA-$^{111}In$ complex binds with serum proteins.

• Bulletin of the Korean Chemical Society
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• v.31 no.3
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• pp.678-682
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• 2010

A doubly tethered chiral stationary phase (CSP) based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid were applied to the liquid chromatographic resolution of racemic tocainide, an antiarrhythmic agent, and its analogues. The chiral recognition efficiency of the doubly tethered CSP for tocainide and its analogues was generally greater than that of the corresponding singly tethered CSP especially in terms of the resolution ($R_S$). The resolution of tocainide and its analogues on the doubly tethered CSP were dependent on the content and the type of the organic and acidic modifiers in aqueous mobile phase and the column temperature. Especially, the retention behaviors of analytes on the doubly tethered CSP with the variation of the content of organic modifier in aqueous mobile phase were opposite to those on the corresponding singly tethered CSP and these opposite retention behaviors were rationalized by the lipophilicity differences of the two CSPs.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.65-76
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• 1992

The superoxide dismutase (SOD)-mimetic activities of copper complexes of a series of salicylic acid (SA) analogs were tested and compared to the activity of bovine erythrocyte SOD using ferricytochrome c reduction assay. Stability constants of copper complexes were measured potentiometrically using SCOGS2 program. In the presence of 10 g/l albumin, all the copper complexes lost their SOD mimetic activities. Multiple regression analysis was employed for the statistical comparisons between the SOD mimetic activity and their physicochemical properties. Correlation exists for the SOD mimetic activity and steric parameter $(E_s)$ and/or electronic parameter $({\Sigma}{\sigma})$ in xanthine/xanthine oxidase (XOD) system, demonstrating that E, plays a key role in SOD activity whereas ${\Sigma}{\sigma}$ influences it to a lesser extent. The protective effect of copper complexes against membrane damage was measured by counting D-glucose released frm $EG_s$. D-glucose and XOD were entrapped within $EG_s$ and acetaldehyde was used as a substrate for XOD. In this membrane model system using $EG_s$, hydrophobic parameter $({\Sigma}{\pi})$ is of most importance, producing parabolic equation while $E_s$, and ${\Sigma}{\sigma}$ appear to playa minor role in protection against D-glucose release. In summary, to design an efficient SOD mimetic, stability, steric factor, lipophilicity and redox potential should be considered.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.95-100
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• 2001

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room temperature. 1-Octanol/water partition coefficients (Log P) and capacity factors (k') were measured to determine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.2
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• pp.1-19
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• 2011

Toxicokinetics of Korean Traditional Medicines(TKM) is the description of what rate TKM will enter the body and what happens to it once it is in the body in terms of toxicology. However, it is not easy to understand TKM toxicokinetics because of various factors such as a mixture of 2-30 kinds of herbal materials containing thousands of chemicals, and complex chemical properties. For these reasons, little is known about toxicokinetics of TKM. This study was aimed to characterize and review the absorption, distribution and metabolism of korean traditional medicines in a view of toxicokinetics. For this aim, some of korean traditional medicines were reviewed on a basis of drug-drug interaction, biotransformation and intestinal metabolisms by bacteria. As the factors affecting mainly on toxicokinetics of TKM, individual herbal material's degree of lipophilicity and metabolic rate, and decoction components according to different kinds of herbal materials were considered. Other factors such as intestinal pH and bacterial activity for metabolism affecting on TKM toxicokinetics, especially in small intestine. It would be a better way for improving the adverse or poor effects caused by TCM if the factors affecting on toxicokinetics of TKM is considered.

• BMB Reports
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• v.38 no.4
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• pp.407-413
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• 2005

Calcium and zinc binding protein, calprotectin is a multifunctional protein with broad spectrum antimicrobial and antitumoural activity. It was purified from human neutrophil, using a two-step ion exchange chromatography. Since surface hydrophobicity of calprotectin may be important in membrane anchoring, membrane penetration, subunits oligomerization and some biological roles of protein, in this study attempted to explore the effect of calcium in physiological range on the calprotectin lipophilicity. Incubation of human calprotectin ($50\;{\mu}g/ml$) with different calcium concentrations showed that 1-anilino-8-naphthalene sulfonic acid (ANS) fluorescence intensity of the protein significantly elevates with calcium in a dose dependent manner, suggesting an increase in calprotectin surface hydrophobicity upon calcium binding. Our study also indicates that calcium at higher concentrations (6, 8 and 10 mM) induces aggregation of human calprotectin. Our finding demonstrates that the starting time and the rate constant of calprotectin aggregation depend on the calcium concentration.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.249-255
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• 1998

Solid Lipid Nanoparticle(SLN), one of the colloidal carrier systems, has many advantages such as good biocompatibility, low toxicity and stability. In this paper, the effects of drug lipophilicity and surfactant on the drug loading capacity, particle size and drug release profile were examined. SLNs were prepared by homogenization of melted lipid dispersed in an aqueous surfactant solution. Ketoprofen, ibuprofen and pranoprofen were used as model drugs and tweens and poloxamers were tested for the effect of surfactant. Mean particle size of prepared SLNs was ranged from 100 to 150nm. The drug loading capacity was improved with the most lipophilic drug and low concentration of surfactant. Particle size and polydispersity of SLNs were changed according to the used lipid and surfactant. The rates of drug release were controlled by the loading drug and surfactant concentration. SLN system with effective drug loading efficiency and proper particle size for the intravenous or oral formulation can be prepared by selecting optimum drug and surfactant.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.495-501
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• 2004

A series of N-substituted-1,3-isoindolinedione derivatives (2-16) were synthesized for the purpose of defining the effect of N-substitution on the anticonvulsant activity of these derivatives. The target compounds (2-16) were obtained by condensation of phthalic anhydride with the corresponding amine derivative. The structures of the synthesized derivatives (2-16) were confirmed by means of IR, $^1$H-NMR, $^{13}$ C-NMR, MS and elemental analyses. The anticonvulsant activity of all compounds (2-16) were evaluated by subcutaneous pentylenetetrazole seizure threshold test at doses of 0.2, 0.4 and 0.8 mmol/kg compared with sodium valproate as a positive control. Their neurotoxicity were determined by the rotorod test. Many of the present series of compounds showed good anticonvulsant activity at the tested doses, as compared to sodium valproate. Three of them (4, 6 and 11) exhibited 100 % protection against convulsions, neurotoxicity and death at all tested doses. Out of the series, two compounds (12 and 13) were completely inactive with 100% mortality. 3-(p-chlorophenyl)-4-(1 ,3-dioxo-2,3-dihydro-1 H-2-isoindolyl) butanoic acid derivative (11) has emerged as the most active compound which is 20 times more active than valproate with ED$_{50}$ 8.7, 169 mg/kg; TD$_{50}$ 413, 406 mg/kg and PI 47.5, 2.4. The results revealed the importance of the combination of baclofenic and phthalimide moieties (compound 11) as a promising anticonvulsant candidate.

• Bulletin of the Korean Chemical Society
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• v.27 no.2
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• pp.211-218
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• 2006

This work deals with 24 substances composed of nitrogen-containing heterocycles. The relationships between the chromatographic retention factor (k) and those physicochemical properties which are relevant in quantitative structure-properties relationship (QSPR) studies, such as the polarizability $(\alpha)$, molar refractivity (MR), lipophilicity (logP), dipole moment $(\mu)$, total energy $(E_{tot})$, heat of formation $(\Delta H_f)$, molecular surface area $(S_M)$, and binding energy $(E_b)$, were investigated. The accuracy of the simple linear regressions between the chromatographic retention and the descriptors for all of the compounds was satisfactory (correlation coefficient, $0.8 \leq r \leq 1.0$). The QSPR models of these nitrogen-containing heterocyclic compounds could be predicted with a multiple linear regression equation having the statistical index, r = 1.000. This work demonstrated the successful application of the multiple linear approaches through the development of accurate predictive equations for retention factors in liquid chromatography.