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유기 음이온계 약물의 간내 이행과정에 있어서 Cytoskeleton의 역할에 관한 속도론적 연구
정연복,한건,육동연,Chung, Youn-Bok,Han, Kun,Yuk, Dong-Yeon 한국약제학회 1992 Journal of Pharmaceutical Investigation Vol.22 No.1
The effects of colchicine on the plasma elimination and biliary excretion of various organic anions in rats were examined. Elimination of indocyanine green (ICG) or rose bengal (RB) from plasma was significantly delayed when rats were treated with colchicine (3 mg/kg body weight) 3 hr prior to the administration of the dye. On the other hand, disappearance of sulfobromophthalein (BSP) or bromophenol blue (BPB) from plasma was not influenced by colchicine. The plasma disappearance and biliary excretion of organic anions were kinetically analyzed based on a compartment model, in which the deep compartment and the unknown disposition are incorporated. The transfer rate constants of ICG or RB, $k_{23}$ (from the liver to the deep compartment) and $k_{3B}$ (from the deep compartment to the bile), were decreased by colchicine, but those of BSP or BPB were not changed. A mechanism for the decrease in the $k_{23}$ and $k_{3B}$ values for ICG and RB might be explained by a inhibition of colchicine to the intracellular cytoskeleton. The hepatocellular distribution of RB or BPB was then determined. BPB mainly distributed to the cytosolic fraction, but RB distributed to each hepatocyte organelle. Taken together. it was suggested that ICG or RB is transported through hepatocytes into bile with the aid of the cytoskeleton, whereas BSP or BPB is handled by hepatocytes in a different way.
한방제제 ( 쌍화탕 ) 가 생체 장기의 소실능력 및 분포성에 미치는 영향에 관한 약물속도론적 연구
정연복,심창구,이민화,김신근 ( Youn Bok Chung,Chang Koo Shim,Min Hwa Lee,Shin Keun Kim ) 생화학분자생물학회 1986 BMB Reports Vol.19 No.1
Consecutive administration (P.O.) of Ssang Wha Tang (SWT), a blended Chinese herbal remedy, caused the increase in the systemic clearance (CL_S) and distribution volume at steady-state (Vd_(ss)) of bromosulfophthalein (BSP) and aatipyrine in healthy rats as like in CCl₄-treated rats. SWT did not affect the binding of the drugs to plasma proteins. Assuming that hepatic plasma flow (Q) was not affected by SWT administration, the increase in hepatic intrinsic clearance CL^h_(int) could explain the increase in CLS. The increase in CLS seemed not to be the result of the enhanced enzyme activity for hepatic metabolism of the drugs, but to be the result of increased distribution of the drugs to the liver. In conclusion, SWT seemed to enhance the distribution of some drugs to well-stirred organs like liver and therefore enhare the hepatic elimination of the drugs through metabolism.
Effect of a Chinese Herbal Remedy, Ssang Wha Tang, on Distribution and Elimination of Drugs in Rats
정연복,심창구,이민화,김신근,Chung, Youn-Bok,Shim, Chang-Koo,Lee, Min-Hwa,Kim, Shin-Keun 생화학분자생물학회 1986 한국생화학회지 Vol.19 No.1
저자등은 쌍화탕이 손상된 간의 기능을 회복시키며, 특히 간 장해 rat에 주사된 BSP의 클리어란스($CL_s$)와 말초 콤파트멘트의 분포용적 ($V_p$) 을 각각 증가시킴을 보고한 바 있다. 이번에는 정상적인 rat에 있어서 BSP 및 antipyrine의 체내동태에 대한 쌍화탕의 영향을 약물속도론적으로 연구하였다. 그 결과 쌍화탕은 건강한 rat에 투여된 BSP의 $V_p$와 $CL_s$ 및 antipyrine의 체순환 콤파트멘트의 분포용적 ($V_c$)과 $CL_s$를 유의성있게 증가시켰다. 그러나 쌍화탕은 이들 약물과 혈장 단백간의 결합에 영향을 미치지 않았다. 따라서 간 혈장유량 Q가 쌍화탕 처리에 관계없이 일정하다고 가정하면, $CL_s$의 증가는 결국 간에서의 약물대사능력 즉 고유클리어란스(${CL^h}_{int}$) 의 증가에 기인한다고 생각된다. 이러한 대사능력의 증대는 이들 약물의 대사에 관여하는 효소의 활성이 쌍화탕에 의해 증대되었기 때문이라기 보다는 이들 약물의 간장등으로의 분포성이 증가된 때문으로 추정되었다. Consecutive administration (P.O.) of Ssang Wha Tang (SWT), a blended Chinese herbal remedy, caused the increase in the systemic clearance ($CL_s$) and distribution volume at steady-state ($Vd_{ss}$) of bromosulfophthalein (BSP) and antipyrine in healthy rats as like in $CCl_4$-treated rats. SWT did not affect the binding of the drugs to plasma proteins. Assuming that hepatic plasma flow (Q) was not affected by SWT administration, the increase in hepatic intrinsic clearance ${CL^h}_{int}$ could explain the increase in $CL_s$. The increase in $CL_s$ seemed not to be the result of the enhanced enzyme activity for hepatic metabolism of the drugs, but to be the result of increased distribution of the drugs to the liver. In conclusion, SWT seemed to enhance the distribution of some drugs to well-stirred organs like liver and therefore enhace the hepatic elimination of the drugs through metabolism.
우르소데옥시콜린산 및 케노데옥시콜린산의 베타시클로덱스트린 포접복합체의 물리화학적 특성비교
이승룡,정연복,한건,신재영,Lee, Seung-Yong,Chung, Youn-Bok,Han, Kun,Shin, Jae-Young 대한약학회 1994 약학회지 Vol.38 No.3
Physicochemical properties for the inclusion complex of chenodeoxycholic acid(CDCA) and it's $7{\beta}-hydroxy$ epimer ursodeoxycholic acid(UDCA) with ${\beta}-cyclodextrin({\beta}-CyD)$ were studied. The formation of the complex in the solid state were confimed by polarized microscopy and differential scanning calorimetry(DSC). Proton nuclear magnetic resonance$(^1H-NMR)$spectroscopy showed that CDCA and UDCA form an inclusion complex with ${\beta}-CyD$ in aqueous solution. The 1 : 1 stoichiometry of the complex was dextermined by the continuous variation method. From DSC and $^1H-NMR$ studies, there were not any differences between CDCA and UDCA. Complex of CDCA and UDCA showed increase in solubility and dissolution compared with CDCA and UDCA alone, respectively. Solubility pattern of UDCA complex was pH independent but, CDCA complex was like that of CDCA. Dissolution rate increased markedly in case of UDCA complex compared with CDCA complex, especially in acidic pH value.
Zea mays 불검화추출물을 함유하는 정제의 제제설계 및 평가
한용해,정연복,한건,정석재,박만기,심창구,Han, Yong-Hae,Chung, Youn-Bok,Han, Kun,Chung, Suk-Jae,Park, Man-Ki,Shim, Chang-Koo 대한약학회 2000 약학회지 Vol.44 No.6
The purpose of the present study was to design and prepare the optimum formulation for the oral administration of titrated extract of the unsaponifiable fraction of Zea mays L. (ETIZM). For this purpose, we simulated the blood concentration of ETIZM after its oral administration, changing the dissolution rate constants $(0.05{\sim}20\;hr^{-1})$. In vivo parameters, such as absorption rate constant $(k_a)$, elimination rate constant (k) and volume of distribution (Vd), were incorporated in the simulation on the basis of the experiments and literatures. When the dissolution rate constant $(k_r)$ is over $5\;hr^{-1}$, the absorption process appears to be the rate limiting step for the transport of ETIZM from the G.I. ract to the blood circulation. While less than $5\;hr^{-1}$, the dissolution rate considered to be the rate limiting step. Moreover, the optimum blood concentration was shown in the range from 1 to $5\;hr^{-1}$ of $k_r$ in the simulation. To design and prepare the tablets on the basis of the above results, 7 formula containing HPMC, PEG 4000 and PEG 6000 (1-5%, respectively) were prepared and evaluated. The tablets containing PEG 4000 (1%), PEG 6000 (1%) or PEG 4000 (5%) satisfy the optimum $k_r$ range ($1-5\;hr^{-1}$). These formulations, therefore, will be able to show the more effective blood concentration, compared with the commercial products after the oral administration.
서방성 $Cephalexin-Eudragit^{\circledR}$ 마이크로캅셀의 생물약제학적 평가
한건,김광덕,정연복,지웅길,김신근,Han, Kun,Kim, Kwang-Dug,Chung, Youn-Bok,Jee, Ung-Kil,Kim, Shin-Keun 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.2
Microcapsules(Mc) of cephalexin (CEPH), using Eudragit RS, RL, L, S and polyethylene glycol 1540, were evaluated biopharmaceutically. The area under the curve of CEPH-Eudragit RS/RL Mc administered orally once was larger than that of cephalexin powder twice every 6 hrs. Controlledrelease effectiveness and the absorption rate effectiveness, two important parameters of Vallner's method, of CEPH-Eudragit RS/RL Mc indicate that these Mc can be good sustained-release preparations. And a simple pharmacokinetic model is introduced which allows the gastric emptying and intestinal-transit rates of a drug itself and a solid-state drug contained in Mc. Decreasing $K_r$, without change in $K_a$, showed that the rate-limiting step of absorption moved from absorption step to releasestep.