음이온계 약물의 간수송과정에 있어서 대향수송의 약물동력학적 모델링 및 시뮬레이션

송석길(Sukgil Song),이준섭(Jun Seup Lee),정연복(Youn Bok Chung) 대한약학회 2005 약학회지 Vol.49 No.4

The purpose of the present study was to kinetically investigate the carrier-mediated uptake in the hepatic transport of organic anions, and to simulate the "in vivo counter-transport" phenomena, using kinetic model which was developed in this study. The condition that the mobility of carrier-ligand complex is greater than that of free carrier is not essential for the occurrence of "counter-transport" phenomenon. To examine the inhibitory effects on the initial uptake of organic anions by the liver, it is necessary to judge whether the true counter-transport mechanism (trans-stimulation) is working or not. Effects of bromophenol blue (BPB) or bromosulfophthalein (BSP) on the plasma disappearance curves of a 1-anilino-8-naphthalene sulfonate (ANS) were then kinetically analyzed based on a flow model, in which the ligand is eliminated only from the peripheral compartment (liver compartment). Moreover "in vivo counter-transport" phenomena were simulated based on the perfusion model which incorporated the carrier-mediated transport and the saturable intracellular binding. The "in vivo counter-transport" phenomena in the hepatic transport of a organic anions were well demonstrated by incorporating the carrier-mediated process. However, the "in vivo counter-transport" phenomena may be also explained by the enhancement of back diffusion due to the displacement of intracellular binding. In conclusion, one should be more cautious in interpreting data obtained from so-called "in vivo counter-transport" experiments.

신규 피리미딘 구조를 함유한 항바이러스성 화합물 CPD의 수용약중 가용화

송석길(Sukgil Song),권호석(Ho Seok Kweon),정연복(Youn Bok Chung) 대한약학회 2006 약학회지 Vol.50 No.1

The purpose of the present study was to formulate the aqueous solution of 1-cyclopent-3-enylmethyl-6(3,5-dimethyl-benzoyl)-5-ethyl-1H-pyrimidine-2,4-dione (CPD), a novel antivirus compound containing pirimidine structure. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants (Tween 80, Cremophor?? RH40, Cremophor?? EL, Poloxamer 407, Poloxamer 188) and complexation agent [hydroxypropyl-β-cyclodextrin (HPBCD)], on the solubility of CPD in aqueous solution were evaluated. The solubility of CPD in water was under 1 ㎍/㎖ at 20℃. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of CPD at the 0~40% concentration range. The solubility of CPD was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, Cremophor?? L, Cremophor?? RH40, and HPBCD showed enhanced effects on the solubility of CPD. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the CPD solubility were less pronounced compared with tween 80, Cremophor?? L or Cremophor?? RH40. As a results, tween 80 aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 20% tween 80 were formulated as a dosing solution containing CPD for its intraperitoneal and intrahypodermic administration, respectively. The formular showed physical stability after stored for 7 days at 4℃. Keywords : CPD, solubility, stability, cosolvent, surfactant

신규 항암성 화합물 아크리플라빈과 구아노신 복합체를 흰쥐에 근육주사시 아크리플라빈의 체내분포

송석길(Sukgil Song),정연복(Youn Bok Chung) 대한약학회 2006 약학회지 Vol.50 No.1

A 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a does of 30 ㎎/㎏ ACF in rats. To analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the sample were linear over the concenration range of 0.05~200 ㎍/㎖. The intra- and inter-day assay accuracies of this method were within ±15% of norminal values and the precision did not exceed 15% of relative standard diviation. The lower limits of quantitation were 50 ng/㎖ for both TRF and PRF. The distribution of TRF or PRF was determined by 48h after i.m. administraion of the combination mixture at a dose of 30㎎/㎏ ACF. TRF and PRF were distributed as the followeing order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12h after i.m. administration were not detected. The number of the platelets in the 1㎖ of the blood was calculated to be 0.183×108/㎖ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24h after i.m. administraion of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24h after i.m. administration of the combination mixture at a dose of 30 ㎎/㎏ ACF.

HIV-1 치료제로서 chemokine 수용제 저해제

이재권, 송석길, 이종길 충북대학교 약품자원개발연구소 2006 약학논문집 Vol.21 No.-

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GM-CSF blocks the resiquimod-induced differentiation of myeloid-derived suppressor cells into macrophages and dendritic cells

이문규, 임선아, 송석길, 이청길 충북대학교 약품자원개발연구소 2013 약학논문집 Vol.28 No.-

Myeloid-derived suppressor cells (MDSCs) accumulate in cancer patients and tumor-bearing mice and suppress the host immune system. MDSCs represent a group of immature myeloid cells that express CD11b and Gr-1. Recently, we showed that the TLR agonist resiquimod, which binds to TLR7 and TLR8, induces the differentiation of MDSCs into mature macrophages and dendritic cells (DCs). Here we report that the differentiation-inducing activity of resiquimod is blocked by granulocyte mammary carcinoma 4T1 cells, and then cultured with resiquimod for three days in the presence or absence of GM-CSF. Phenotypic analysis showed that the MDSCs cultured in the presence or resiquimod differentiated into F4/80+ macrophages, and CD11c+/Ⅰ-Ad+ DCs. The resiquimod-induced differentiation of MDSCs into mature myeloid cells, however, was almost completely adjuvant for vaccines for patients with cancers in whom MDSCs play a major role in the suppression of anti-tumor immune responses.

SSD1과 상호작용하는 유전자

성혜란, 배윤진, 송나리, 이종길, 송석길 충북대학교 약품자원개발연구소 2006 약학논문집 Vol.21 No.-

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당단백 erythropoietin (EPO)의 약물학적 응용

성스런, 손동주, 박미희, 송석길, 윤도영, 오기완, 한건, 문동철, 홍진태 충북대학교 약품자원개발연구소 2004 약학논문집 Vol.19 No.-

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대장균에서 D - Ribose 의 저친화성 수송에 관여하는 유전자

김창훈,박찬규,송석길 한국유전학회 1996 Genes & Genomics Vol.18 No.4

Mutants defective in the high-affinity transport of D-ribose are able to utilize ribose as a sole carbon and energy source, suggesting that other low-affinity transport systems for the sugar exist in the cells. In order to search for these transport systems, transposon mutagenesis was performed. Mutants with different phenotypes on ribose minimal growth were observed and classified into five groups. The precise locations of insertions on the chromosome were determined by in vivo cloning and analysis using polA mutation. Group I insertions revealed an operon encoding a new ABC-type transporter, located in 92.8 min. Group II insertions lie in rbs operon with defective growth on ribose due to a polar inactivation of rbsK, the gene for ribokinase. Group III insertion was found in the open reading frame, f547 coding for a potential integral membrane protein similiar to the proton symporter XylE. Insertions in xylA and its promoter region (Group IV) enhanced the growth on ribose, which was abolished by secondary insertion (Group V) in xylG gene that is divergently transcribed from xylA. XylG protein appears to be a component of the high affinity transporter for D-xylose. This indicates that the high affinity D-xylose transport system also supports the uptake of D-ribose.

Resiquimod, a TLR7/8 agonist, promotes differentiation of myeloid-derived suppressor cells into macrophages and dendritic cells

이민규,박찬수,이영란,임선,송석길,이종길 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.9

Myeloid-derived suppressor cells (MDSCs)accumulate in cancer patients and tumor-bearing mice, subsequentlysuppressing the host immune system. MDSCsrepresent a group of immature myeloid cells expressingCD11b and Gr-1. Here, we show that a Toll-like receptor(TLR) agonist, resiquimod, which binds to TLR7 and TLR8,induces the differentiation of MDSCs into mature myeloidcells. MDSCs were isolated from mice bearing mammarycarcinoma 4T1 cells, and the purified MDSCs were culturedin the presence of resiquimod for 5 days. Phenotypic analysisshowed that the resiquimod-treated MDSCs differentiatedinto F4/80? macrophages and CD11c?/I-Ad? dendritic cells. Functional analysis showed that the MDSCs also lost theirsuppressive activity on T cells. Resiquimod-treated MDSCssignificantly enhanced the proliferation of T cells that weretreated with anti-CD3 and anti-CD28 monoclonal antibodies. These results show that resiquimod induces the differentiationofMDSCs into macrophages and dendritic cells, and alsosuggest that resiquimod may improve cancer immunotherapyby reducing immunosuppressive MDSCs.

主要 논雜草 올챙이고랭이와 사마귀풀 生態에 關한 硏究

金昭年(Kim, S. Y),宋錫吉(S. G. Song),金鳳九(B. G. Kim) 韓國雜草學會 1985 Weed&Turfgrass Science Vol.5 No.2