• Title/Summary/Keyword: Drug Distribution

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Copolymerization of N-Vinyl Pyrrolidone with Functionalized Vinyl Monomers: Synthesis, Characterization and Reactivity Relationships

  • Vijaykumar, S.;Prasannkumar, S.;Sherigara, B.S.;Shelke, N.B.;Aminabhavi, Tejraj M.;Reddy, B.S.R.
    • Macromolecular Research
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    • v.17 no.12
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    • pp.1003-1009
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    • 2009
  • Copolymers of N-vinylpyrrolidone (NVP) comonomer with styrene (St), hydroxypropyl methacrylate (HPMA) and carboxyphenyl maleimide (CPMI) were synthesized by free radical polymerization using 2,2'-azobisisobutyronitrile (AIBN) initiator in 1,4-dioxane solvent. The copolymers formed were characterized by FTIR, $^1H$ NMR and $^{13}C$ NMR techniques and their thermal properties were studied by DSC and TGA. Copolymer composition was determined by $^1H$ NMR and/or by elemental analysis and monomer reactivity ratios (MRR) were estimated by the linear methods of Kelen-Tudos (K-T) and extended Kelen-Tudos (EK-T) and the non-linear approach. Copolymers of St and HPMA with NVP formed blocks of one of the monomer units, whereas alternating copolymers were obtained in CPMI-NVP, depending upon the side chain substitution. The MRR values are discussed in terms of monomer structural properties such as electronegativity and electron delocalization. The sequence distribution of monomers in the copolymers was studied by statistical method based on the average reactivity ratios obtained by EK-T method.

The study about Sasang Constitution diagnosis and research trends in the case reports (증례논문에 나타난 사상체질진단의 특징 및 연구동향에 대한 연구)

  • Ban, Duk-Jin;Lee, Seung-Yun;Park, Seong-Sik
    • Journal of Sasang Constitution and Immune Medicine
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    • v.21 no.2
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    • pp.107-114
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    • 2009
  • 1. Objectives : We analyzed the case reports published by the journal of Sasang Constitutional Medicine, to study Sasang Constitution diagnosis and characteristic of clinical practice. 2. Methods : It has been examined 138 case reports of Sasang Constitution society published from 1994 to 2008. We analyzed. patient's number, publication year, distribution of Sasang Constitution, title's characteristics and bases of constitution diagnosis. 3. Results and conclusions : 1) In the analysis of patient's number, 1 case report was almost part of the case reports, and the case reports ware many published after 2001. 2) In the analysis distribution of Sasang Constitution, Soyangin was the most Sasang Constitution, and Tae-umin was the next one and Soeumin, Taeyangin followed them. 3) In the analysis of the journal's title, Sasang Constitution, disease and symptom of Sasang Constitution were more important than prescription recently. 4) In the analysis of the journal's purpose, unique disease and response of treatment were almost part of the case reports. 5) In the analysis of diagnosis bases, subjective bases were more important than objective bases and Sasang Constitutional drug response. therefore we should do researches in objective bases and drug response in the future.

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A Study on KASP Analysis Based on SNP to Rapidly Identify Caviar-Producing Sturgeon Species (캐비어를 생산하는 철갑상어의 신속 종판별을 위한 SNP 기반 KASP 분석에 관한 연구)

  • Sun Hee Lee;Bo Reum Park;Hyung Il Kim;Sooyeul Cho;Kyung-Hun Son
    • Journal of Food Hygiene and Safety
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    • v.39 no.3
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    • pp.209-220
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    • 2024
  • Cavier is graded as Beluga, Osetra, and Sevruga based on the species of sturgeon (Acipenser sinensis). In this study, we developed an analytical method for determining the grade of black caviar using DNA barcodes and KASP markers. To identify the sturgeon species, ten black caviar samples were collected, and a reference DNA barcode library was developed using five genes (namely, 16S ribosomal RNA, cytochrome b, cytochrome c oxidase subunit I, cytochrome c oxidase subunit II, and NADH dehydrogenase subunit 5 genes). To develop the KASP markers, we selected 11 markers that could distinguish between the five grades of black caviar. As a result, specific markers for each of the targeted caviars were clustered into FAM-positive sections. DNA barcoding and the KASP assay revealed that one Beluga, six Osetra, and three Sevruga were identified among the ten caviar samples. Moreover, we found that the sturgeon species were mislabeled in two products. Here, we aimed to develop a KASP assay based on SNP that allows rapid and easy identification of caviar grade. These methods are expected to contribute to preventing the distribution of illegal products.

Development of Detection Method for Niphon spinosus, Epinephelus bruneus, and Epinephelus septemfasciatus using 16S rRNA Gene (16S rRNA를 이용한 다금바리, 자바리, 능성어 판별법 개발)

  • Park, Yong-Chjun;Jung, Yong-Hyun;Kim, Mi-Ra;Shin, Joon-Ho;Kim, Kyu-Heon;Lee, Jae-Hwang;Cho, Tae-Yong;Lee, Hwa-Jung;Lee, Sang-Jae;Han, Sang-Bae
    • Korean Journal of Food Science and Technology
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    • v.45 no.1
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    • pp.1-7
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    • 2013
  • Niphon spinosus, Epinephelus bruneus, and Epinephelus septemfasciatus are involved in the Perciformes Order and Serranidae Family. When E. bruneus and E. septemfasciatus are fully grown, the striped pattern on the body gradually disappears. Therefore, morphological classification of adult fishes is quite difficult to identify the differences to N. spinosus. In this study, we investigate the method to differentiate those using PCR. To design the primers, 16S rRNA region of N. spinosus, E. bruneus, and E. septemfasciatus registered in the GeneBank (www.ncbi.nlm.nih.gov) have been used and for the analysis, Bio Edit ver. 7.0.9.0 was used. As a result, it was design NS-003-F/NS-005-R (136 bp), EB-001-F/EB-002-R (181 bp), and ES-001-F/ES-001-R (123 bp) primers for the differentiation of each 3 different fishes. Therefore, the species-specific primer sets would be a useful tool for scientific and speedy differentiation against the illegal distribution for consumer protection.

EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models

  • Yan, Feng;Bai, Li-Ping;Gao, Hua;Zhu, Chang-Ming;Lin, Li;Kang, Xiang-Peng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2619-2623
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    • 2014
  • Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

Preparation and Evaluation of Bupivacaine Microspheres by a Solvent Evaporation Method (용매증발법에 의한 부피바카인 microsphere의 제조 및 평가)

  • Kwak, Son-Hyok;Hwang, Sung-Joo;Lee, Byung-Chul
    • YAKHAK HOEJI
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    • v.44 no.6
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    • pp.511-520
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    • 2000
  • Various bupivacaine-loaded microspheres were prepared from poly (d,l-lactide) (PLA) or poly (d,l-lactic-co-glycolide) (PLGA) by a solvent evaporation method for the sustained release of drug. PLA and PLGA microspheres were prepared by w/o/w and w/o/o multiple emulsion solvent evaporation, respectively. The effects of process conditions such as emulsification speed, emulsifier type, emulsifier concentration and internal/external phase ratio on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their drug loading, size distribution, surface morphology and release kinetics. Drug loading efficiency was higher in the microspheres prepared by w/o/o multiple emulsion than that by w/o/w multiple emulsion method, because the solubility of bupivacaine HCI was decreased in oil phase compared with water phase. The prepared microspheres had an average diameter between 1 and $2\;{\mu}M$ in all conditions of two methods. In morphology studies the PLA microspheres showed an irregular shape and smooth surface, but PLGA microspheres had a spherical shape and smooth surface. The release pattern of the drug from microspheres was evaluated on the basis of the burst effect and the extent of the release after 24h. The in vitro release of bupivacaine HCl from microspheres showed a large initial burst release and $60{\sim}80%$ release within one day in all conditions of two methods. The extents of the burst release against PLA and PLGA microspheres were $30{\sim}50%$ and $50{\sim}80%$ within 20min, respectively. This burst release seems to be due to the smaller size of microspheres and the solubility of drug in water.

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Population Pharmacokinetics of Midazolam in Healthy Koreans: Effect of Cytochrome P450 3A-mediated Drug-drug Interaction (건강한 한국인에서 미다졸람 집단약동학 분석: CYP3A 매개 약물상호작용 평가)

  • Shin, Kwang-Hee
    • Korean Journal of Clinical Pharmacy
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    • v.26 no.4
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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.

Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Daniel M. Miller
    • Korean Journal of Microbiology
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    • v.38 no.4
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    • pp.203-203
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    • 2002
  • Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

Characterization of Physicochemical Properties of Ferulic Acid

  • Sohn, Young-Taek;Oh, Jin-Hee
    • Archives of Pharmacal Research
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    • v.26 no.12
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    • pp.1002-1008
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    • 2003
  • Ferulic acid (3-methoxy, 4-hydroxy cinnamic acid) is a flavoid component possessing antioxidant property. The compound is currently under development as a new drug candidate for the treatment of the dementia. The objective of this preformulation study was to determine the physicochemical properties of ferulic acid. The n-octanol to water partition coefficients of ferulic acid were 0.375 and 0.489 at the pHs of 3 and 10, respectively. Accelerated stability study for ferulic acid indicated that the t 90 value for the drug was estimated to be 459 days at $25^{\circ}C$. Ferulic acid was also found to be unstable under the relative humidity of more than 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of ferulic acid with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1: 1 binary mixtures of ferulic acid and typical pharmaceutical excipients (e.g., Aerosil, Avicel, CMC, Eudragit, lactose, PEG, PVP, starch and talc). Avicel, CMC, PVP and starch were found to be incompatible with ferulic acid, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of ferulic acid powder was in the size range of 10-190 $\mu$m with the mean particle size of 61 $\mu$m. The flowability of ferulic acid was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Two polymorphic forms were obtained by recrystallization from various solvents used in formulation. New polymorphic form of ferulic acid, Form II, was obtained by recrystallization from 1,4-dioxane. The equilibrium solubility for Form I was approximately twice of that for Form II. The dissolution rate of Form II was higher than that of Form I in the early phase (<6 min). Therefore, these physicochemical information has to be taken in the consideration for the formulation of ferulic acid.

Optimization and Applicability Verification of Simultaneous Chlorogenic acid and Caffeine Analysis in Health Functional Foods using HPLC-UVD (HPLC-UVD를 이용한 건강기능식품에서 클로로겐산과 카페인 동시분석법 최적화 및 적용성 검증)

  • Hee-Sun Jeong;Se-Yun Lee;Kyu-Heon Kim;Mi-Young Lee;Jung-Ho Choi;Jeong-Sun Ahn;Jae-Myoung Oh;Kwang-Il Kwon;Hye-Young Lee
    • Journal of Food Hygiene and Safety
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    • v.39 no.2
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    • pp.61-71
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    • 2024
  • In this study, we analyzed chlorogenic acid indicator components in preparation for the additional listing of green coffee bean extract in the Health Functional Food Code and optimized caffeine for simultaneous analysis. We extracted chlorogenic acid and caffeine using 30% methanol, phosphoric acid solution, and acetonitrile-containing phosphoric acid and analyzed them at 330 and 280 nm, respectively, using liquid chromatography. Our analysis validation results yielded a correlation coefficient (R2) revealing a significance level of at least 0.999 within the linear quantitative range. The chlorogenic acid and caffeine detection and quantification limits were 0.5 and 0.2 ㎍/mL and 1.4, and 0.4 ㎍/mL, respectively. We confirmed that the precision and accuracy results were suitable using the AOAC validation guidelines. Finally, we developed a simultaneous chlorogenic acid and caffeine analysis approach. In addition, we confirmed that our analysis approach could simultaneously quantify chlorogenic acid and caffeine by examining the applicability of each formulation through prototypes and distribution products. In conclusion, the results of this study demonstrated that the standardized analysis would expectably increase chlorogenic acidcontaining health functional food quality control reliability.