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김종국,김경미,권수연 ( Chong Kook Kim,Kyoung Mi Kim,Soo Yeon Kwon ) 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.2
N/A Epidermal growth factor (EGF) is a mitogen which activate the proliferation of basal cells in skin, which implicate the wound healing in severe skin damage such as burn. To carry out the preclinical test for the pharmacological action of EGF, EGF in transdermal delivery system must be stable. Since EGF is a protein susceptible to proteolysis and unstable in aqueous solution, in vitro stabilization of EGF is prerequisite for the formulation. In this study, effect of additives on the stability of EGF is investigated in vitro. The stability of EGF in aqueous solution was enhanced with the various water-soluble polysaccharides such as HPMC, sorbitol. mannitol and dextrin. EGF was successfully extracted from the ointment with 5% HPMC solution, and EGF in aqueous solution and ointment was also successfully stabilized with 5% HPMC. The ointments prepared with different amount of EGF were applied on the damaged dorsal skin of rats for the determination of optimal concentration of EGF. The ointment with EGF (10 ㎍/g) showed good wound healing action on the damaged skin of rats.
제산제와 항궤양제 복합제제의 In Vitro 및 In Vivo 제산력 평가
김종국,안혜진,정은주,오경희,나운용,Kim, Chong-Kook,Ahn, Hye-Jin,Jeong, Eun-Joo,Oh, Kyung-Hee,Lah, Woon-Lyong 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.4
The combined products of antacid and anti-ulcer agent were prepared with antacid composed of aluminium hydroxide dried gel, magnesium hydroxide and simethicone with a ratio of 1:1:0.1 (M) and anti-ulcer agent, aceglutamide aluminium (AGA). The efficacy of antacid was evaluated in vitro with Fuchs, Johnson-Duncan and Rosset-Rice methods and in vivo using an aspiration method in rat. The addition of anti-ulcer agent did not affect the neutralizing capacity of M significantly. The combined products with the M/AGA ratios of 2.3:1 and 3.4:1 produced the maximum pH of $4.0{\sim}5.8$ and the duration time of $64{\sim}137$ min in vitro test. The in vivo neutralizing test in rats showed the rapid increase of gastric pH up to 3.5 within 30 min and the gastric pH of $4{\sim}6$ was kept for 5 hr.
김종국,황수원,황성주,나운용,Kim, Chong-Kook,Hwang, Su-Won,Hwang, Sung-Joo,Lah, Woon-Lyong 한국약제학회 1989 Journal of Pharmaceutical Investigation Vol.19 No.2
In order to develop a pediatric liquid preparation with sustained release properties, dextromethorphan hydrobromide (DEXT) was complexed with strong cation exchange resin (CG 120) and the-complex was coated with Eudragit RS using a phase separation method by non-solvent addition. The effect of pH, ionic strength of the release medium and drug/resin ratio on the release rate of DEXT was studied. The release rate of free drug from the uncoated complex, and coated complexes with 9.5 and 18.5% Eudragit RS in artificial gastric juice were measured. The release rate from the uncoated complex was faster with higher pH, higher ionic strength of the release medium and higher drug/resin ratio. The release rate from the coated complex could be controlled by the amount of coating material, and the surface after release did not rupture into.
은행잎엑스 수용액 중 Gingkoflavonglycoside의 안정성
김종국,박만기,이은진,황성주,Kim, Chong-Kook,Park, Man-Ki,Lee, Eun-Jin,Hwang, Sung-Joo 한국약제학회 1989 Journal of Pharmaceutical Investigation Vol.19 No.4
To formulate the stable preparation of Gingko extract injection and to evaluate the stability of the preparation, Gingko extract aqueous solutions having various pH values were prepared and the stability of ginskoflavonglycoside (GFG) was investlfated by high performance liquid chromatography. The stability of GFG decreased as pH increased, while the water solubility of Gingko extract decreased as pH decreased. The optimal pH of the Gingko extract aqueous solution was found to be pH 6.5. The shelf life $(T_{90%})$ of the Gingko extract aqueous solution of pH 6.5 at $20^{\circ}C$ was extrapolated to be four years.
김종국,이범진,Kim, Chong-Kook,Lee, Bum-Jin 대한약학회 1988 약학회지 Vol.32 No.3
We measured the rate of water transfer across the isolated small intestine of the rat in Wiseman apparatus using tritiated water ($^3H_2O$) in drinking beverages such as electrolytes solution, fruit juice, carbonated water and barley water. Initial transfer rate of water using four beverages were determined: Electrolytes solution is the fastest and followed by barley water, carbonated water and fruit juice.
김종국,정은주,이은진,신희종,이원근,Kim, Chong-Kook,Jeong, Eun-Ju,Lee, Eun-Jin,Shin, Hee-Jong,Lee, Won-Keun 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.1
The bioequivalence of two omeprazole enteric-coated products was evaluated in 16 normal male volunteers (age 26-32 yr, body weight 57-75 kg) following single oral administration. Test product was enteric-coated KD-182 tablet (Chong Kun Dang Corp., Korea) and reference product was $Rosec^{\circledR}$ capsule containing enteric-coated pellets of omeprazole (Yuhan Corp., Korea). Both products contain 20 mg of omeprazole. One tablet or capsule of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study ($2\;{\times}\;2$ Latin square method). Average drug concetrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products(p>0.05); the area under the concentrationtime curve to last sampling time (8 hr) $(AUC_{0-8hr})$ $(1946.5{\pm}675.3\;vs\;2018.3{\pm}761.6\;ng{\cdot}hr/ml)$, AUC from time zero to infinite $(AUC_{o-\infty})$ $(2288.6{\pm}1212.8\;vs\;2264.9{\pm}1001.3\;ng{\cdot}hr/ml)$, maximum plasma concentration $(C_{max})$ $(772.5{\pm}283.3\;vs\;925.8{\pm}187.7\;ng/ml)$, time to maximum plasma concentration $(T_{max})$ $(2.38{\pm}1.06\;vs\;2.34{\pm}1.09\;hr)$, apparent elimination rate constant $(k_{\ell})$ $(0.5339{\pm}0.2687\;vs\;0.5769 {\pm}0.2184\;hr^{-I})$, apparent absorption rate constant $(k_a)$ $(1.1536{\pm}0.5278\;vs\;0.9739{\pm}0.9507 hr^{-1})$ and mean residence time (MRT) $(3.13{\pm}0.73\;vs \;3.41{\pm}1.04\;hr)$. The differences of mean $(AUC_{0-8hr})$, $C_{max}$, $T_{max}$ and MRT between the two products (3.69, 19.83, 1.32 and 8.99%, respectively) were less than 20%. The power $(1-{\beta})$ and treatment difference $(\triangle)$ for $AUC_{o-8hr}$ $C_{max}$ and MRT were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different each other(p>0.05). These results suggest that the bioavailability of KD-182 tablet is not significantly different from that of $Rosec^{\circledR}$ capsule. Therefore, two products are bioequivalent based on the current results.
[3H]-메토트렉세이트-락토오스아미노화한 소 혈청 알부민 공유결합체의 간표적성 및 체내동태
김종국(Chong Kook Kim),이응두(Woong Doo Lee),박호군(Ho Koon Park) 대한약학회 1992 약학회지 Vol.36 No.6
The organ distribution of [3H]-methotrexate-lactosaminated bovine serum albumin conjugates ([3H]-MTX-LBSA) was investigated to examine their role as a liver-specific anticancer drug. Synthesis of lactosaminated bovine serum albumin(LBSA) with BSA, lactose and sodium cyanoborohydride through reductive animation was followed by its conjugation with methotrexate (MTX) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), thereby synthesizing [3H]-MTX-LBSA conjugates. Organ distribution and plasma elimination profiles were studied in male Wistar rats after intravenous injection of [3H]-MTX-LBSA conjugates. The fates of [3H]-MTX and the [3H]-MTX-BSA conjugates fates were also investigated for comparison. The results showed that the plasma level of [3H]-MTX-LBSA conjugates declined more rapidly than those of [3H]-MTX-BSA and their liver concentration was significantly higher than those of other treatment (p<0.01). In addition, their uptake compared to the amount taken up by the liver (1 : 33.1 at 10min, 1 : 24.1 at 120min). All these suggested that MTX-LBSA conjugate is one of the drug delivery system (DDS) that is advanced in concentrating MTX in the liver and minimizing the renal toxicity of MTX.
김종국(Chong -Kook Kim),원용한(Young Han Won),양지선(Ji Sun Yang),임연수(Yun Su Lim),안혜영(Hae Young Ahn) 한국약제학회 1983 Journal of Pharmaceutical Investigation Vol.13 No.1
Binding of ibuprofenlysine with bovine serum albumin was studied and compared by fluorescence quenching method, difference spectroscopy and circular dichroism. These spectrophotometric methods are indirect measurements which need the probes. So 1-anilinonaphthalene-8-sulfonate was used as a fluorescence spectra probe, 2-(4` hydroxybenzeneazo) benzoic acid as a difference spectrophotometric probe, and sulfaethidole was used as a circular dichroism probe. The results by above three methods were compared and discussed.
김종국(Chong Kook Kim),최한곤(Han Gon Choi) 大韓藥學會 1997 약학회지 Vol.41 No.5
Peonjahwan composed of crude herb, and materials and tissue of animals is a considerably bitter and poorly water-soluble oriental medicine for the treatment of hepatitis. Peonja dry elixir and Eudragit-coated peonja dry elixir were prepared using spray-dryer to mask the bitterness and enhance the release of ingredients from peonjahwan. The bitterness of peonja dry elixir and Eudragit-coated peonja dry elixir reduced to 1/2 and 1/4 of that from peonja powder, respectively. Furthermore, the release rate of bound bilirubin from dry elixir was significantly higher than that from peonja powder.
김종국(Chong Kook Kim),이사원(Sa Won Lee),최한곤(Han Gon Choi),고종호(Zhong Gao Gao),이미경(Mi Kyung Lee),김인숙(In Sook Kim) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.2
The bioequivalence of two clarithromycin products was evaluated with 16 normal male volunteers (age 23-28 yr, body weight 57.5-75.5 kg) following single oral dose. Test product was ReYon Clarithromycin tablets (ReYon Pharm. Corp., Korea) and reference product was Klaricid^R tablets (Abbott Korea). Both products contain 250 mg of clarithromycin. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2 x 2 Latin square method). The determination of clarithromycin was accomplished using a modified agar well diffusion bioassay. As a result of the assay validation, the quantification of clarithromycin in human serum by this technique was possible down to 0.03 ㎍/ml using 100 ㎕ of serum. The coefficient of variation (C.V.) was less than 10%. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve to last sampling time (24 hr) (AUC_(0→24h)) (8.10 ±1.26 vs 8.22 ±1.62 ,㎍/ml), AUC from time zero to infinite (AUC_(0→∞)) (8.61 ±1.28 vs 8.84 ±1.71 ㎍ ·hr/ml), maximum plasma concentration (C_(max)) (0.87 ±0.22 vs 0.88 ±0.19 ㎍/ml) and time to maximum plasma concentration (T_max) (2.69 ±0.48 vs 2.56 ±0.51 hr). The differences of mean AUC _(0→24h), C_(max) and T_(max) between the two products (1.44, 1.39, and 4.65%, respectively) were less than 20%. The power (1-β) and treatment difference (△) for AUC _(0→24h), and C_(max) were more than 0.8 and less than 0.2, respectively. Although the power for T_(max) was under 0.8, T_(max) of the two products was not significantly different each other (p>0.05). These results suggest that the bioavailability of ReYon Clarithromycin tablets is not significantly different from that of Klaricid^R tablets. Therefore, two products are bioequivalent based on the current results.