• 약학회지
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• 제28권3호
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• pp.161-167
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• 1984

To improve the solubility properties of indomethacin, a poorly water-soluble drug, some attempts were made with surfactants, such as sodium deoxycholate, sodium laurylsulfate and polysorbate-80. The enhancement effect in solubility was found to be due to the micellar solubilization and dependent on the concentration of surfactants, pH and temperature. The mechanism of interaction was suggested to be attributed to the formation of mixed micelles between the drug and solubilizers.

• Archives of Pharmacal Research
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• 제1권1호
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• pp.13-20
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• 1978

Alcohol extracts of plants widely used in the traditional medicine have been tested to establish if they affect the metabolism of drug in mice. Forteen of the plants tested exhibited prolonging and/or inhibitory effect on hexobarbital sleeping time. Some of them also showed increasing effect on strychnine mortality, whereas piperis retrofracti Fructus reduced the toxicity of strychnine.

• Toxicological Research
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• 제34권1호
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• pp.23-29
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• 2018

Ethanol-induced fat accumulation, the earliest and most common response of the liver to ethanol exposure, may be involved in the pathogenesis of liver diseases. Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a chalcone derivative that exhibits antioxidant, anti-inflammatory, and phytoestrogenic activities. However, the effect of ISL treatment on lipid accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore, we evaluated the effect and underlying mechanism of ISL on ethanol-induced hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL ($0{\sim}50{\mu}M$) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$) was studied by western blotting. Our results indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP-1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a decrease in ethanol-induced fat accumulation upon co-treatment of ethanol-treated cells with 10, 20, and $50{\mu}M$ of ISL. These findings suggest that ISL can reduce ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus improve lipid metabolism in alcoholic fatty livers.

• 한국임상약학회지
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• 제26권4호
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Archives of Pharmacal Research
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• 제16권2호
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• pp.129-133
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• 1993

Temperature sensitive liposomes(TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drug, Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature $(T_c)$ of TSL was dependent on the lipid compositions of TSL ADM broadened thermogram of TSL but Ara-C did not. However, $T_c$ of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near $T_c$ and observed at $39-41^\circ{C}$ for DPPC (Dipalmitoylphosphatidylcholine) only, $52-54^\circ{C}$ for DPPC and DSPC (1:1), respectively. Effect of human serum alburmin (HAA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below $T_c$. However, ADM release from TSL was increased at the near and above $T_c$. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near TEX>$4^\circ{C}$. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at TEX>$4^\circ{C}$ was not changed, the TSL was considered to be stable for at least 1 week at TEX>$4^\circ{C}$. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.

• Archives of Pharmacal Research
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• 제29권12호
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• pp.1179-1186
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• 2006

Cross-linked starch microspheres were prepared using different kinds of cross-linking agents. The influence of several parameters on morphology, size, swelling ratio and drug release rate from these microspheres were evaluated. These parameters included cross-linker type, concentration and the duration of cross-linking reaction. Microspheres cross-linked with glutaraldehyde had smooth surface compared with those prepared with epichlorhydrine or formaldehyde. The particle size increased with increasing the cross-linking time and increasing the drug loading. Swelling ratio of the particles was a function of cross-linker type but not the concentration or time of cross-linking. Drug release from starch microspheres was measured in phosphate buffer and also in phosphate buffer containing a-amylase. Results showed that microspheres cross-linked with epichlorhydrine released all their drug content in the first 30 minutes. However, cross-linking of the starch microspheres with glutaraldehyde or formaldehyde decreased drug release rate. SEM and drug release studies showed that cross-linked starch microspheres were susceptible to the enzymatic degradation under the influence of alpha-amylase. Changing the enzyme concentration from 5000 to 10,000 IU/L, increased drug release rate but higher concentration of enzyme (20,000 IU/L) caused no more acceleration.

• 대한간호학회지
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• 제37권3호
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• pp.295-304
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• 2007

Purpose: This study was conducted to develop an education program for safe drug use in the rural elderly and to measure the effect of the program. Method: This study utilized a nonequivalent control group pretest-posttest design. The subjects of this study consisted of 40 older persons who were more than 65 years old and lived in G and C moon, Y gun, Gyeongsang-bukdo and visited the public health subcenter. Twenty were assigned to the experimental group and 20 to the control group. The education was provided for one and a half hours, once a week for 3 weeks. Data was collected before, right after, and one month after the program. Result: The first hypothesis was supported(F=79.24, p=0.000) showing that the knowledge scores of the drug use of the experimental group were significantly higher than those of the control group at post education and one month after education. The second hypothesis was supported(F=23.84, p=0.000) showing that the drug misuse and abuse prevention behavior scores in the experimental group were significantly higher than those of the control group at post education and one month after the education. Conclusion: This study suggests that the education for safe drug use is effective in promoting knowledge and behavior for safe drug use of the rural elderly.

• Natural Product Sciences
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• 제20권2호
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• pp.130-134
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• 2014

An investigation was carried out to identify novel anti-cancer compounds from Korean indigenous plant extracts. Bioassay-guided fractionation and chemical investigation of the EtOAc extract from the leaves and stems of Stauntonia hexaphylla resulted in the isolation of two active compounds, hederagenin 3-O-${\alpha}$-L-arabinoside (1) and quercetin (2). The structures of these compounds were elucidated by spectroscopic methods, including UV, IR, MS, NMR techniques and compared with previous spectroscopic data. The cytotoxic effects of fractions and compounds on HCT116 human colon cancer cells were evaluated using the MTT assay. Quercetin showed a stronger anti-cancer effect when compared to hederagenin 3-O-${\alpha}$-L-arabinoside.

• KSBB Journal
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• 제10권4호
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• pp.461-467
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• 1995

본 연구에서는 약물 전달체(키토산, 키토산.엽, 술폰화키토산)에 prednisolone을 분산시켜 제조한 고분자 매트릭스를 poly (DL-lactide)로 피막을 형성시킨 후 pH 1.2와 pH 7.4 인산염 완충용액에서 약물 방출실험을 하였다. 약물 방출시간은 pH 1.2에서 보다 pH 7.4에서 더 지연되였으며 약물 전달체의 함유량이 증가함에 따라 약물의 방출시간도 지연되었다. 피막된 고분자 매트릭스의 종류에 따라 지연된 약물의 방출시간은 키토산의 경우가 가장 길었으 며, 술폰화키토산, 키토산.염의 순셔였다. Monolith IC 고분자 매트릭스에 비해 2배 정도의 약물의 방출 지연성을 보인 피막된 monolithic 고분자 매트럭스 가 방출조절형 제제로서 더 바람직한 것으로 관찰되었다. 이러한 제형들은 초기 급격한 약물 방출속도의 변화를 억 제 하는 sustained release pattern 제 제 임을 확인할 수 있었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.179-179
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• 2003

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanisms of TCDD-induced carcinogenesis are poorly understood, it considered to be non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1).(omitted)