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          • SCIESCOPUSKCI등재

            Determination of Recombinant Human Epidermal Growth factor (rhEGF) in a Pharmaceutical Preparation by Capillary Electrophoresis

            Hwang,,Kyung-Hwa,Lee,,Kang-Woo,Kim,,Chang-Soo,Han,,Kun,Chung,,Youn-Bok,Moon,,Dong-Cheul The Pharmaceutical Society of Korea 2001 Archives of Pharmacal Research Vol.24 No.6

            A simple assay method of recombinant human epidermal growth factor (rhEGF) in a pharmaceutical preparation was studied and validated by capillary electrophoresis (CE) using micellar electrokinetic chromatography (MEKC) techniques. Factors affecting the migration behavior and separation performances of the peptide; type of buffers pH, butler concentration, and concentration of sodium dodecyl sulfates (SDS) were investigated to optimize the analytical performance. CE was performed using running buffers 50.0 mM borate (pH 8.5) containing 12.5 mM SDS at 20 $mutextrm{V}$ of the applied voltage. Calibration curves for the rhEGF showed good linearity (r>0.999) over the wide dynamic range from 1.25 to $100{\mu\textrm{g}}/ml$. Sample analysis was performed by using standard addition method to eliminate the matrix effects of dosage vehicle. This method is assumed to be useful for quality control (QC) of various forms of pharmaceutical products of the peptide.

          • SCIESCOPUSKCI등재

            Current trends in benzodiazepine research

            Klinger,,M. The Pharmaceutical Society of Korea 1982 Archives of Pharmacal Research Vol.5 No.1

            Thank you for inviting me as a guest speaker to this 30th anniversary of the Pharmaceutical Society of Korea. I take it as a compliment to may firm F. Hoffmann-La Roche and Co., Which, has not only dicovered and introduced the benzodiazepines, but has since then been continually in the fore-front of this research. As may subject is going to be "Current Trends in Benzodiazepine Research" I will try to have a look into pending problems. The history of the benzodiazepines has been told several times (e. g. Sternbach, Haefely).

          • SCIESCOPUSKCI등재

            Cytotoxic activities of various fractions extracted from some pharmaceutical insect relatives

            Huang,,Yao-Ge,Kang,,Jong-Koo,Liu,,Ren-Song,Oh,,Ki-Wan,Nam,,Chun-Ja,Kim,,Hack-Seang The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.2

            This research was performed to screen the cytotoxic activities of some pharmaceutical insect relatives. Cytotoxic activities of total extract and fractions of hexane, ethyl acetate, methanol, water and boiling water were extracted from four pharmaceutical insect relatives: the Chinese gall, the cicada slough, the hornet nest and the batryticated silkworm. These extracts were investigated against the cancer cell lines of L1210, P388 and SNU-1 in vitro tests. Results showed that, ED, , against the cancer cell lines of L1210, P388 and SNU-1 were 0.55, 0.50, and $0.83{\mu}g/ml$ in the ethyl acetate fraction from the Chinese gall; 1.07, 2.19, and $2.24{\mu}g/ml$in the ethyl acetate fraction, 1.51, 1.26, and $1.45{\mu}g/ml$ in the water fraction and 1.48, 2.29, and $1.29{\mu}g/ml$in the boiling water fraction from the cicada slough; 3.31, 2.00, and $6.61\mug/ml$ in the water fraction from the hornet nest and 13.80, 19.95, and $31.62{\mu}g/ml$in the hexane fraction and 33.88, 21.88, and $25.12{\mu}g/ml$in the ethyl acetate fraction from the batryticated silkworm, respectively. All of the fractions mentioned above showed high cytotoxic activities and could be suggested for further studies in vivo tests.

          • SCIESCOPUSKCI등재

            The Anti-Fibrogenic Effect of a Pharmaceutical Composition of[5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (Oltipraz) and Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB)

            Kang,,Keon-Wook,Kim,,Yoon-Gyoon,Kim,,Choon-Won,Kim,,Sang-Geon The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.5

            Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

          • SCIESCOPUSKCI등재

            Determination of Recombinant Human Epidermal Growth factor (rhEGF) in a Pharmaceutical Formulation by High Performance Liquid Chromatography with Electrochemical Detection

            Lee,,Kang-Woo,Hwang,,Kyung-Hwa,Kim,,Chang-Soo,Han,,Kun,Chung,,Youn-Bok,Park,,Jeong-Sook,Lee,,Yong-Moon,Moon,,Dong-Cheul The Pharmaceutical Society of Korea 2001 Archives of Pharmacal Research Vol.24 No.4

            A novel HPLC method with electrochemical detection has been developed for the determination of recombinant human epidermal growth factor (rhEGF) in pharmaceutical products. rhEGF was separated from other components in formulation on a reversed-phase C18 column with 24% acetonitrile in 0.1 M phosphate buffer (pH 4.75). The optimum electrochemical oxidation of EGF was obtained at 0.85 V vs. Ag/AgCl in a glassy carbon working electrode due to electroactive tyrosine, tryptophan, methionine, and arginine residues. The quantitation range was from 1.0 to 200 ng of rhEGF with the linear correlation coefficient greater than 0.999. The method was successfully applied for the quantitation of rhEGF in a pharmaceutical preparation.

          • SCIESCOPUSKCI등재

            Development of Controlled Release Oral Drug Delivery System by Membrane-Coating Method-I - Preparation and pharmaceutical evaluation of controlled release acetaminophen tablets-

            Shim,,Chang-Koo,Kim,,Ki-Man,Kim,,Young-Il,Kim,,Chong-Kook The Pharmaceutical Society of Korea 1990 Archives of Pharmacal Research Vol.13 No.2

            In order to develop a controlled-release oral drug delivery system (DDS) which sustains the plasma acetaminophen (AAP) concentration for a certain period of time, microporous membrane-coated tablets were prepared and evaluated in vitro. Firstly, highly water-soluble core tablet of AAP were prepared with various formulations by wet granulation and compression technique. Then the core tablets were coated with polyvinychloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of core tablets and coating suspensions on the pharmaceutical characteristics such as drug release kinetics and membrane stability of the coated tablets was investigated in vitro. AAP was released from the coated tablets as a zero-order rate in a pH-independent manner. This independency of AAP release to pH change from 1.2 to 7.2 is favorable for the controlled oral drug delivery, since it will produce a constant drug release in the stomach and intestine regardless of the pH change in the GI tract. Drug release could be extended upto 10 h according to the coating condition. The release rate could be controlled by changing the formula compositions of the core tablets and coating suspensions, coat weight per each tablet, and especially PVC/sucrose ratio and particle size of the sucrose in the coating suspension. The coated tablets prepared in this study had a fairly good pharmaceutical characteristics in vitro, however, overall evaluation of the coated tablet should await in vivo absorption study in man.

          • SCIESCOPUSKCI등재

            Protein Drug Oral Delivery: The Recent Progress

            Lee,,Hye-J. The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.5

            Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.

          • SCIESCOPUSKCI등재

            Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole

            Heo,,Min-Young,Piao,,Zong-Zhu,Kim,,Tae-Wan,Cao,,Qing-Ri,Kim,,Ae-Ra,Lee,,Beom-Jin The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.5

            Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

          • SCIESCOPUSKCI등재

            Pharmaceutical studies on the polymorphism of hydrochlorothiazide

            Kim,,Bong-Hee,Kim,,Johng-Kap The Pharmaceutical Society of Korea 1984 Archives of Pharmacal Research Vol.7 No.1

            Four polymorphic forms (I, II, III and IV) of hydrochlorothiazide have been characterized on the basis of x-ray diffractometry and differential thermal analysis. Form I was obtained by crystallization from N, N-dimethylformamide and Form II was crystallized from hot methanol. Form III was precipitated from sodium hydroxide aqueous solution by treatment with hydrochloric acid and Form IV was crystallized from 50% methanol. The metastable form I was a most stable form among four polymorphs, which was stable more than ten months at room temperature. The thermodynamic parameters such as heat of solution, enthalpy, entropy, free energy difference and transition temperature were determined by the measurement of intrinsic dissolution rate. The transition temperature and the heat of transition between the metastable Form I an Form II were determined to be $299.15^{\circ}$K and 5.03 Kcal/mole, respectively and free energy difference ($\delta$ F) was 302. 13 cal/mole. Diuretic action of these four polymorphic forms was also evaluated by monitoring the difference in urinary excretion of sodium, potassium and magnesium in rats.

          • SCIESCOPUSKCI등재

            Pharmaceutical Studies on Chitosan Matrix: Controlled release of aspirin from chitosan device

            Lee,,Chi-Young,Kim,,Sung-Ho The Pharmaceutical Society of Korea 1987 Archives of Pharmacal Research Vol.10 No.2

            Chitosan ($\beta$-D-glucosaminan) is chemically prepared from chitin (N-acetyl-$\beta$- D-glucosaminan) which is an unutilized natural resource. We now report on the suitability of the chitosan matrix for use as vehicles for the controlled release of drugs. Salicylic acid and aspirin were used as model drugs in this study. The permeation of salicylic acid in the chitosan membranes was determined in a glass diffusion cell with two compartments of equal volume. Drug release studies on the devices were conducted in a beaker containing 5% sodium hydroxide solution. Partition coefficient (Kd) value for acetate membrane (472) is much greater than that for fluoro-perchlorate chitosan membrane (282). Higher Kd value for acetate chitosan membrane appears to be inconsisstent with the bulk salicylic acid concentration. The permeability constants of fluoro-perchlorate and acetate chisotan membranes for salicylic acid were 3.139 ${\times}10^{-7}cm^2$ min up to 60 min and that of 30% aspirin in the devices was 4.739${\times}10^{-7}cm^2$sec upto 60 min. As the loading dose of aspirin in a chitosan device increased, water up-take of chitosan device increased, but in case of salicylic acid it decreased. The release rate increased with increase in the molecular volume of the drugs. Thses result suggest that the release mechanism may be controlled mainly by diffusion through pores.

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