큰눈물버섯 등 한국산 담자균류의 렉틴 활성

정경수,정연주 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

As an effort to develop noble antitumor lectins from Korean basidiomycetes, wild mushrooms were collected and their cold-water extracts were subjected to a screening test for their lectin activities using hemmagglutination assay on BALB/c mouse erythrocytes. Of the nine species tested, three species, Psathyrella velutina, Fomitella fraxinea and Russula compacta, showed strong hemmagglutinating activities, while the other six species showed minimal or no activities. Of these, partial purification of the lectin components of P. velutina and R. compacta were attempted by precipitation with saturated ammonium sulfate followed strong hemmagglutination activity unlike that of R. compacta, which lost its lectin activity after the purification process. Moreover, the partially purified P. velutina lectin exerted cytotoxic effect on sarcoma 180 cells when assessed by flow cytometric analysis.

비페닐 디메틸 디카르복실레이트(DDB)의 용출향상을 위한 고체분산체의 제조 및 평가

이정우,김정수,이계원,지웅길 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

Biphenyl dimethyl dicarboxylate(DDB) is synthetic compound derived from Schizandrin C, a component of Fructus Schizandrae. DDB is currently employed as an agent against virally induced hepatic injury and has been found to be effective in improving liver function and symptoms of patients with chronic viral hepatitis. But, DDB is practically water-insoluble and its dissolution rate is extremely low, resulting in very low bioavailability(20-30%). To improve the dissolution rate of DDB, solid dispersion particles of DDB were prepared with two different types of hydrophilic polymers such as Eudragit E100, hydroxypropylmethylcellulose(HPMC) by spray drying method. Properties of solid dispersions were characterized by DSC and PXRD. DDB tablets were prepared by compressing the powder mixtures composed of raw DDB, solid dispersions, lactose and Avicel PH102, magnesium stearate. At ratio above 1:3(w/w), DDB was amorphous state within DDB-Eudragit E100 solid dispersion. As the weight ratio of Eudragit E100 to DDB was increased, the dissolution rate of DDB-Eudragit E100 solid dispersion tablets was reached 69.37-98.29% after 30min. But, it rapidly decreased to 28.34-45.98% after 2hour due to precipitation of DDB. However, in case of 1:3:1 DDB-Eudragit E100-HPMC solid dispersion tablet containing HPMC, dissolution rate was reached 97.47% after 2hour without decrease of dissolution rate. From overall findings, DDB formulation containing Eudargit E100 and HPMC solid dispersion could be used to remarkably improve the dissolution rate in dosage form of tablets.

한국인 지원자에서 니모디핀의 생체이용율연구

강원호,심희옥,남진경,김동출 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

A reversed phase HPLC method was developed and validated for the determination of nimodipine in human plasma. Nitrendipine was used as an internal standard. Calibration curves were linear in the concentration range of 5~300 ng/ml. The coefficient of variation of the intra- and inter-day precision was below 15%. The coefficient of variation of the accuracy was below 15% in the concentration range investigated. A bioavailability study was performed using the validated HPLC method. Eight healthy male volunteers were orally administered 30 mg of nimodipine. The pharmacokinetic parameters were calculated using WinNonlin. The mean values of AUC_(24hr) was 64.0±31.3 ng·hr/ml, C_(max) was 46.5±31.2 ng/ml, T_(max) was 0.54±0.17 hr and t_(1/2) was 3.03±2.26 hr. The pharmacokinetic parameters and the HPLC method can be used for the design of bioequivalence study of nimodipine.

Causes responsible for the in vivo reduction of activity of paraoxonase 1, a detoxifying enzyme of anticholinesterase organophosphates

Sok, Dai-Eun 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

Paraoxonase 1(PON1), which is well known to hydrolyze organophosphates such as paraoxon and nerve agents, is widely distributed in blood, liver, heart, kidney as well as brain. Also, mRNA for PON1 was detected in a number of tissues apart from the liver, suggesting a possible role for this protein family. Initial investigation of PON1 focused on its ability to hydrolyze organophosphate compounds, playing a major role in the detoxification of these compounds. Recent interest in the enzyme has arisen from the observations that they possess antioxidant action against copper ion-catalyzed oxidation of lipids or proteins. Such an antioxidant action could contribute to further augment the benefit of paraoxonase1 in preventing against organophosphate poisoning, especially accompanied by oxidative stress. Therefore, it is important to maintain PON1 activity in vivo. Above all, it has been of a curiosity to find the causes responsible for the loss of PON1 activity, and provide the measures to prevent against the reduction of PON1 level. The mechanisms responsible for the in vivo inactivation of PON1 by oxidative conditions will be reviewed. In addition, the inhibition of PON1 activity by endogenous factors including negatively-charged lipids will be addressed. Further, the strategy to preserve the activity of paraoxonase 1, a detoxifier of anticholinesterase organophosphates, in vivo system will be discussed. Finally, there will be a discussion on the possible common function of two hydrolases, acetylcholinesterase and paraoxonase 1, in preventing oxidative stress.

염산 독세핀 외용제의 피부 전달 시스템을 위한 제제 설계 및 평가

이은미,김정수,경기열,이계원,지웅길 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

Doxepin hydrochloride(Dox) is a dibenzoxepin-derivative tricyclic antidepressant and used topically for the short-term relief of moderately severe pruritus associated with atopy dermatitis. Dox topical emulsion(or liposome) formulations were evaluated with respect to their rheological properities, permeation through excised skin of hairless mouse and in vitro/in vivo accumulation in the skin. The apparent viscosity was increased according to the concentration of glycerin and decreased with an increase in the concentration of phosphatidylcholine(PC). The permeation rate of formulation increased with a high concentration of PC and showed no relationship with the change of formulations. Amount of accumulated drug in the excised skin of hairless mouse was decreased with a high concentration of glycerin, but increased according to PC concentration.

이종 장기 이식을 위한 다단계 거부 반응의 조절

이광수,김영관,박희진,이재오,명평근 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

The transplantation of organ, tissues or cells between individuals of different species has been of increasing interest in recent years because the use of animals as organ and tissue donors as a source of transplants would overcome the severe and worsening shortage of human organs available for transplantation. However, There are some major hurdles to the clinical application of xenotransplantation; the immunologic response of the recipient against donor, the physiology of the graft, and the possibility that a xenotransplant might transmit an infection from the source to the recipient. This review describes the unique aspects of the immunological barrier to transplanting organs from non-primates such as pigs into humans, focusing especially on the mechanisms which contribute to immunorecognition, physiology of the rejection and infectious hurdles to xenotransplantation. This communication might be applied to overcoming these hurdles and the possibility that genetic strategies might be used to expand the potential applications of xenotransplantation for the treatment of human disease.

Tacrolimus의 LC/MS 분석과 지원자에 대한 약물동태 연구

윤민혁,이서판,남진경,권광일 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

The purpose of this study was to confirm the analysis method and also to estimate the pharmacokinetic parameters of tacrolimus in human volunteers. The pharmacokinetics of tacrolimus tablet was examined on 24 healthy volunteers who received a single oral dose(4mg) of each preparation in the fasting state. After an oral dosing, blood samples were collected for a period of 72 hours. Blood concentrations of tacrolimus were determined using a liquid chromatographic electrospray mass spectrometric (LC-MS) method. The pharmacokinetic parameters were calculated with non-compartmental(AUC, C_(max), T_(max), Cl_(t), V/F) and compartmental(K_(el), K_(a), K_(12), K_(21), t_(1/2)) pharmacokinetic analysis using WinNonlin program. The estimated means of AUC_(0-72hours), C_(max) and T_(max) were 425.54 ± 197.49 ng·hr/ml, 76.14 ± 29.18 ng/ml and 1.40 ± 0.44 hr, respectively. The means of other pharmacokinetic parameters(V/F, CL_(t), K_(el), K_(a), K_(23), K_(32) and t_(1/2)) were 35.12 ± 34.28 L, 10.45 ± 5.32 L/hr, 0.39 ± 0.21 hr^(-1), 1.91 ± 4.17 hr^(-1), 0.32 ± 0.33 hr^(-1), 0.07 ± 0.09 hr^(-1), 26.94 ± 10.19 hr^(-1), respectively.

염산 메트폴민을 함유하는 경구방출제어형 제제의 제조 및 용출특성

구본철,김정수,이계원,지웅길 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

Metformin is an antihyperglycemic agent of the biguanide class used in the treatment of non-in-sulin-dependent diabetes mellitus. Metformin hydrochloride has intrinsically poor permeability in the lower portion of the GI-tract leading to absorption almost exclusively in the upper part of the GI-tract. Its oral bioavailability is in the range of 50 to 60%. It also has a very high water solubility. In this study, we prepared sustained release matrix system containing metformin hydrochloride using various characteristics of polyethylene oxide (PEO). The metformin hydrochloride matrix tablets were prepared by direct compressed method and wet granulation compressed method with various molecular weight of PEO. Even though the molecular weights of PEOs used were 900K, 2,000K, and 5,000K. Moreover, three types of matrix tablets were formulated compositions were same, the hardness was different. The release kinetics were studied for 9 hours in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, using a dissolution tester at 37.5℃, 50 rpm. As the molecular weight of PEO increased, the release rate decreased due to the slower swelling and dissolution of PEO. For the effect of hardness of matrix tablets, the rate of drug release was decreased with increasing hardness.

이트라코나졸 경구제제의 제제설계 및 평가

장혜진,김정수,이계원,지웅길 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

We prepared oral formulations of itraconazole by hot-melt process to increase dissolution rate of this drug. Oral liquid preparations of drug were prepared by melt method with lactic acid and blended with co-solvent, antioxidant and surfactant. Glycofurol and isopropyl alcohol were used as co-solvents, and ascorbic acid and as-corbyl palmitate were used as antioxidants, and TPGS and Gelucire 44/14 were used as surfactants. The final preparations contained 10% of itracnoazole as drug content percentage. The dissolution profiles of itraconazole from liquid preparation were determined at 37±0.5℃ at a stirring rate of 100 rpm using the paddle method. The oral absorption of itraconazole liquid preparation was studied in the rabbits. Major pharmacokinetic parameters (AUC_(0-48hr), C_(max), T_(max)) were calculated from the plasma concentration-time data. The dissolution rate of itraconazole was higher for itraconazole liquid preparation filled into a hard gelatin capsule with 90% release within 20min as compared to 20% for Sporanox capsules. Both the AUC_(0-48hr) and C_(max) values of liquid formulation prepared with isopropyl alcohol were higher than those of itraconazole prepared with glycofurol. The dissolution rate of itraconazole liquid preparation was higher as compared to Sporanox capsules. The bioavailability of drug prepared with isopropanol were higher than those of drug prepared with glycofurol.

Total oxy-radical scavenging capacity assay를 이용한 taurine과 hypotaurine의 항산화 활성 측정

오정민,주홍매,김상겸,김봉희 忠南大學校 生命科學硏究院 醫藥品開發硏究所 2006 藥學論文集 Vol.21 No.-

Taurine, a sulfur containing non-amino acid, is one of the most abundant intracellular amino acid in humans, and hypotaurine is a precursor of the synthesis of taurine. While it is widely believed that taurine may play an important role in protecting cells against toxic injury by functioning as an antioxidant, there is a lack of evidence to support this hypothesis. In this study, total oxy-radical scavenging capacity(TOSC) assay was used to evaluate antioxidant activity of taurine and hypotaurine against peroxyl radical, hydroxyl radical and peroxynitrite. The present results show that taurine does not have oxy-radical scavenging activity and hypotaurine is comparable to glutathione, an antioxidant substance, in oxy-radical scavenging activity. The results suggest that protective effects of taurine against oxidative stress may not be associated with its direct oxy-radical scavenging activity. Difference in oxy-radical scavenging capacity between taurine and hypotaurine may be ascribed to their sulfur oxidation state.