• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.207-215
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• 2008

Drug approval-patent linkage is the practice of linking drug marketing approval to the patent status of the originator's product and not allowing the grant of marketing approval to any third party prior to the expiration of the patent term unless by consent of the patent owner. Article 18.9.5 of Korea-US Free Trade Agreement requires that Korea introduce the linkage system in drug marketing approval. However, Korea is unfamiliar with the linkage system. In addition, there have been lots of arguments over the impacts of this system on Korean pharmaceutical industry and pharmaceutical market in the future. This report investigated the linkage systems of the US and Canada. The US and Canada have implemented drug approval-patent linkage system since 1984 and 1993, respectively. Both countries have patent lists for drug approvalpatent linkage on which originators are required to list patents on substance, product, and use of their drugs. Generic or follow-on drug applicants must contain a certification regarding each patent listed that relates to the referenced drug. If the patent holder files suit for patent infringement within 45 days of notice of application, drug approval is not allowed for several months - 30 months in the US and 24 months in Canada. Both countries have amended their systems after having experienced unexpected results such as listing improper and additional patents, multiple patent litigations and delayed generic entries. After reviewing the US and Canada's experiences, we suggested three principles needed in implementing the system: protecting patent holder's right; promoting generic drug development and marketing; monitoring the process and the effect of the system.

• Journal of Nutrition and Health
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• v.31 no.5
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• pp.939-948
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• 1998

To investigate the relationship between eating behavior and the prevalence of adolescents drug abuse and smoking, this survey was conducted among 349 male students(mean age ; 16.0 $\pm$0.9yrs) at technical high schools in Kyunggi-Do. It was shown that 58.7% of total subjects were smoking and 11.2% were abusing drugs. Drug abusers weighed Less than non-abusers especially, student smokers were 2.7kg lighter than non-smokers despite the same height. Although parents' education showed no relationship with drug abuse, educational level of student smokers' fathers was significantly lower than that of non-smokers' fathers. Drug abusers and smokers showed significantly higher incidence of runaway from home, absence from school without notice, and parents' divorce than non-abusers and non-smokers. Drugs abused were sleeping pills(n=20), bonds and butane gas(n=9), marijuana(n=3), tranquilizer(n=3), morphine and cocaine(n=2), and pep pills like amphetamine(n=2) 76.9% of the drug abusers had their first experience in junior high school and 81% of the smokers stared smoking as early as in junior high school. Also, 44% of the smokers reported that they smoke daily. The drug abusers tended to have more irregular eating habits than the non-abusers. The smokers showed irregular mealtime, ate either too fast or too slow, and especially, often skipped lunch or dinner. The drug abusers and smokers took little vegetable in their meals and often ate bread or noodles instead of rice for staples. In addition, they preferred taste to nutrition when they had meals. The smokers tended to ingest smaller amount of calcium source such as milk or dinner food and fish with bone although they consume more volume of total foods than the non-smokers. All subjects took less in calorie, calcium, iron, vitamin A, vitamin E, riboflavin, and folic acid than the Recommended Dietary Allowance Those findings suggest that drug abuse and smoking cause bad eating habits that influence unbalanced nutritional state. Therefore, nutrition education should be provided to the adolescents so that they can recognize the disadvantages of drug and smoking and its relation to dietary relation. (Korean J Nutrition 31(5) : 939-948, 1998)

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.339-343
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• 2009

Recently, co-delivery of drug and gene has been attempted for higher therapeutic effects of anticancer agents. In this study, cationic liposomes were prepared using 1,2-dioleoyl-3-trimethylammoniopropane (DOTAP) as a cationic lipid to investigate the effect of drug loading on the physicochemical characteristics of cationic liposomes/DNA complexes. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. Particle size of complexes was reduced not by drug loading, but by the increased ratio of cationic lipid to plasmid DNA. Meanwhile, zeta potential of complex was increased by the addition of cationic liposomes to complexes and the effect of drug loading on the zeta potential was not much higher than on particle size. Gel retardation of complexes was indicated when the complexation weight ratios of cationic lipid to plasmid DNA were higher than 24:1 for drug free complexes and 20:1 for drug loaded ones, respectively. Agarose gel retardation showed the similar complexation between plasmid DNA and drug free liposomes or drug loaded liposomes. Both complexes protected plasmid DNA from DNase independent of complexation temperature. From the results, drug loading may affect not the complex formation of cationic liposomes and plasmid DNA, but the particle size of complex.

• Korean Journal of Environmental Agriculture
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• v.32 no.3
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• pp.207-213
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• 2013

BACKGROUND: This study was conducted to develop analytical method with reproducibility, accuracy and applicability to agricultural products than the existing methods. METHODS AND RESULTS: Mean recoveries of thidiazuron ranged from 89.2 to 91.2 in hulled rices, 87.2 to 92.1 in peppers, from 76.4 to 86.9 in potatoes, from 91.2 to 95.7 in watermelons, from 86.5 to 88.5 in kiwi fruits, and from 89.5 to 94.0 in grapes, with less than 10% of relative standard deviations. In addition, the limit of quantitation was set to be 0.05 mg/kg and there were no interfering peaks in integrating the thidiazuron peak. CONCLUSION(S): These results represent that the enhanced analytical method has reliable accuracy, precision, selectivity, and sensitivity.

• Korean Journal of Environmental Agriculture
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• v.42 no.1
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• pp.71-81
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• 2023

An accurate and easy-to-use analytical method for determining isocycloseram and its metabolites (SYN549431 and SYN548569) residue is necessary in various food matrixes. Additionally, this method should satisfy domestic and international guidelines (Ministry of Food and Drug Safety and Codex Alimentarius Commission CAC/GL 40). Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) was used to determine the isocycloseram and its metabolites residue in foods. To determine the residue and its metabolites, a sample was extracted with 20 mL of 0.1% formic acid in acetonitrile, 4 g magnesium sulfate anhydrous and 1 g sodium chloride and centrifuged (4,700 G, 10 min, 4℃). To remove the interferences and moisture, d-SPE cartridge was performed before LC-MS/MS analysis with C₁₈ column. To verify the method, a total of five agricultural commodities (hulled rice, potato, soybean, mandarin, and red pepper) were used as a representative group. The matrix-matched calibration curves were confirmed with coefficients of determination (R²) ≥ 0.99 at a calibration range of 0.001-0.05 mg/kg. The limits of detection and quantification were 0.003 and 0.01 mg/kg, respectively. Mean average recoveries were 71.5-109.8% and precision was less than 10% for all five samples. In addition, inter-laboratory validation testing revealed that average recovery was 75.4-107.0% and the coefficient of variation (CV) was below 19.4%. The method is suitable for MFDS, CODEX, and EU guideline for residue analysis. Thus, this method can be useful for determining the residue in various food matrixes in routine analysis.

• Animal cells and systems
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• v.1 no.1
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• pp.77-80
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• 1997

DOantrolene is a primary specific therapeutic drug for prevention and treatment of malignant hyperthermia symptoms. The mechanisms underlying the therapeutic effects of the drug are not well understood. The present study aimed at the characterization of the effects of azumolene, a water soluble dantrolene analogue, on ryanodine binding to sarcoplasmic reticulum (SR) from normal and malign::lnt hyperthermia susceptible (MHS) swine muscles. Characteristics of $[^3H]ryanodine$ binding were clearly different between the two types of SR. Kinetic analysis of eH]ryanodine binding to SR in the presence of $2{\mu}M$ $Ca^{2+}$ showed that association constant $(K_{ryanodine}_7$ is significantly higher in MHS than normal muscle SR $(2.83 vs. 1.32{\times}10^7 M^{-1}$, whereas the maximal ryanodine binding capacity $(B_{max})$ is similar between the two types of SR. Addition of azumolene $(e.g. 400{\mu}M)$ did not significantly alter both $K_{ryanodine}$ and $B_{max}$ of $[^3H]$ryanodine binding in both types of SR, indicating that the azumolene effect was not on the ryanodine binding sites. Addition of caffeine activated $[^3H]$ ryanodine binding in both types of SR, and caffeine sensitivity was significantly higher in MHS muscle SR than normal muscle SR $(K_{caffeine}:3.24 vs. 0.82 {\times} 10^2 M^{-l}). Addition of azumolene $(e.g.400{\mu}M)$ decreased Kcaffeine without significant change in $B_{max}$ in both types of SR suggesting that azumolene competes with caffeine binding site(s). These results suggest that malignant hyperthermia symptoms are caused at least in part by greater sensitivity of the MHS muscle SR to the $Ca^{2+}$ release drug(s), and that azumolene can reverse the symptoms by reducing the drug affinity to $Ca^{2+}$ release channels.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.44-50
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• 2020

Background: Drug-drug interactions (DDIs) in patients using oral anticancer treatment are more common than in those using injectable anticancer agents. In addition, DDIs related to anticancer treatment are known to cause clinically significant outcomes, such as treatment failure and severe toxicity. To prevent these negative outcomes, significant DDIs are monitored and managed using the information provided in drug databases. We aimed to evaluate the consistency of information on clinically significant DDIs for tyrosine kinase inhibitors (TKIs) between representative drug databases. Methods: We selected clinically significant DDIs involving medications that are co-prescribed with TKIs and met the following criteria: the severity level of DDIs was equal or greater than "D" in Lexicomp^® or "major" in Micromedex^®. We then analyzed the consistency of the severity classification and evidence level between the drug databases. Spearman's correlation coefficient was used to identify the relationship between DDI information in the drug databases. Results: In total, 627 DDI pairs were identified as clinically significant; information on these was provided by Lexicomp^® and Micromedex^® for 571 and 438 pairs, respectively, and both drug databases provided information on 382 DDI pairs. There was no correlation between the severity and evidence level of DDIs provided in the two databases; Spearman's correlation coefficient for Lexicomp^® and Micromedex^® was -0.009 (p=0.861) and -0.064 (p=0.209), respectively. Conclusion: To judge the significance of DDIs, healthcare providers should consider that the information on DDIs may be different between drug information databases; hence, clinical factors must be considered concurrently.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1164-1170
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• 2006

A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS) was confirmed by IR, $^{1}H-NMR$, MS and UV. The concentrations of triptolide in various samples were determined by reversed-phase high-performance liquid chromatography (HPLC). In this study, the physicochemical and stability profiles of TP-LZM under various conditions were investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma (less than 30% of free triptolide released) and could release triptolide quickly in lysosome (more than 80% of free triptolide released) at $37^{\circ}C$ for 24 h. In addition, the biological activities of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested. The conjugate can effectively reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.

• The KIPS Transactions:PartD
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• v.13D no.7 s.110
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• pp.977-984
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• 2006

This paper is intended to trace and management of drug based on RFID Technology at a circulation market, from manufacturer to end user, of drug. To avoid counterfeit and generic drug and establish of order in the circulation of drug, at the moment of manufacturing, tags for each bottle and each box are tagged. and then from factory to hospital, through whole logistics, e-pedigree for the drug is made and monitored. Using inventory information, it is easy to manage and control stock of drug. In addition to, RFID System enables storing and delivery to be simple, process time to be shortened. As this research is to study of applying RFID to drug, in this paper, standard RFID code for drug is suggested and tried to apply domestic middle win. Finally, the result of tag pattern design and how to tag for the drug based on 90Mhz is proposed

• Toxicological Research
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• v.28 no.3
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• pp.143-149
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• 2012

To prepare measures for practical policy utilization and the control of heavy metals, hazard control related institutions by country, present states of control by country, and present states of control by heavy metals were examined. Hazard control cases by heavy metals in various countries were compared and analyzed. In certain countries (e.g., the U.S., the U.K., and Japan), hazardous substances found in foods (e.g., arsenic, lead, cadmium, and mercury) are controlled. In addition, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) recommends calculating the provisional tolerable weekly intake (PTWI) of individual heavy metals instead of the acceptable daily intake (ADI) to compare their pollution levels considering their toxicity accumulated in the human body. In Korea, exposure assessments have been conducted, and in other countries, hazardous substances are controlled by various governing bodies. As such, in Korea and other countries, diverse food heavy metal monitoring and human body exposure assessments are conducted, and reducing measures are prepared accordingly. To reduce the danger of hazardous substances, many countries provide leaflets and guidelines, develop hazardous heavy metal intake recommendations, and take necessary actions. Hazard control case analyses can assist in securing consumer safety by establishing systematic and reliable hazard control methods.