• 제목/요약/키워드: Drug Toxicity

검색결과 709건 처리시간 0.024초

Development of the 3rd Generation Anticancer Platinum Complex as New Drug

  • Cho, Yong-Baik;Ph. D.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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    • pp.97-102
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    • 2002
  • Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.

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Effect of Dietary Capsaicin on Hepatic Drug-Metabolizing Enzyme Activities in Mice

  • Kim, Jung-Mi;Kim, Dong-Hyun;Choe, Suck-Young;Rina Yu
    • Preventive Nutrition and Food Science
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    • 제3권1호
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    • pp.62-66
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    • 1998
  • The effect of dietary capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) on drug-metabolizing enzyme activities was investigated in mice. Male ICR mice were divided into 4 groups and fed diets containing 0, 5, 20, 100 ppm CAP for 4 seeks. Hepatic drug-metabolizing enzyme activities and serum alanine aminotransferase and aspartate transaminease activities were measured. There was no difference in hepatic alanine aminotransferse and aspartate transaminase activities among the groups. Hepatic microsomal cytochrome P450 in CAP fed groups, but p-nitrophenol hydroxylase and the cytosolic acitivity of glutathione S-transferase activities were decreased in the dietary CAP supplemetned groups compared to the control. These results suggest that the dietary CAP at a low dose differentially modulates drug-metabolizing enzyme acitvities without causing hepatic toxicity.

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Doxorubicin-loaded PEI-silica Nanoparticles for Cancer Therapy

  • Heekyung Park;Seungho Baek;Donghyun Lee
    • Korean Chemical Engineering Research
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    • 제61권4호
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    • pp.570-575
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    • 2023
  • Targeted anticancer drug delivery systems are needed to enhance therapeutic efficacy by selectively delivering drugs to tumor cells while minimizing off-target effects, improving treatment outcomes and reducing toxicity. In this study, a silica-based nanocarrier capable of targeting drug delivery to cancer cells was developed. First, silica nanoparticles were synthesized by the Stöber method using the surfactant cetyltrimethylammonium bromide (CTAB). Increasing the ratio of EtOH in the solvent produced uniformly spherical silica nanoparticles. Washing the nanoparticles removed unreacted residues, resulting in a non-toxic carrier for drug delivery in cells. Upon surface modification, the pH-responsive polymer, polyethyleneimine (PEI) exhibited slow doxorubicin release at pH 7.4 and accelerated release at pH 5.5. By exploiting this feature, we developed a system capable of targeted drug release in the acidic tumor microenvironment.

GOOD LABORATORY PRACTICE -PRINCIPLES AND PRESENT STATUS IN JAPAN

  • Omori, Yoshihito
    • Toxicological Research
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    • 제1권1호
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    • pp.31-41
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    • 1985
  • The Japanese Good Laboratory Practice (GLP) Standard on Drugs was finalized as a guideline and implemented in April, 1983. This standard is intended to ensure the quality and integrity of the data from nonclinical toxicity studies submitted to the Ministry of Health and Welfare in support of applications for approval to manufacture or import new drugs or to be used in the reevaluation of previously approved drugs. The standard includes a guideline for organizational matters, personnel, facility, equipment, testing operation, documentation and conduct of studies. Principles and influences of implementation of Japanese GLP will be discussed briefly in comparison with foreign GLPs.

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Single Dose Toxicity Study of IFN-Rod in Cynomolgus Monkey

  • Kim, Choong-Yong;Heo, Jeong-Doo;Han, Su-Cheol;Seol, Eun-Young;Tarumoto, Yasuo;Kwon, Myung-Sang;Ha, Chang-Su
    • 한국환경성돌연변이발암원학회:학술대회논문집
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    • 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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    • pp.60-60
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    • 2004
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In vitro Antitumor Activity and Nephrotoxicity of Pt(II) Complexes Containing Diaminocyclohexane

  • Hong, Eon-Pyo;Rho, Young-Soo;Jung, Jee-Chang
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.358.2-358.2
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    • 2002
  • Platinum(II) coordination complex(cisplatin) has been currently used as one of the most effective compounds in the treatment of various solid tumors. However. its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. (omitted)

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녹용 물추출물과 항암제의 병용투여에 관한 연구(제 1보) -녹용 물추출물과 cis-Platin 및 Mitomycin C 병용투여에 의한 항암제 부작용 경감효과- (Studies on Combined Usage of Velvet Antler Water Extract and Anti-neoplastic Drugs (I) -Reducing Effect of Velvet Antler Water Extract to the Adverse Actions of cis-Platin and Mitomycin C-)

  • 심상범;김재근;원도희;홍남두;김남재
    • 생약학회지
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    • 제29권2호
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    • pp.93-103
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    • 1998
  • In order to investigate the reducing effect of velvet antler water extract (VAWE) on the toxicity of anti-cancer drug, cis-platin (CDDP) and mitomycin C (MMC), we examined effects of co-administration with VAWE and anti-cancer drugs on their toxicities. We recognized that $LD_{50}$ of CDDP/MMC were increased by co-administration with VAWE and them in mice. It was found that co-administration of VAWE and MMC increased the survival rate in mice treated by lethal dose of MMC. Also, co-administration of VAWE and CDDP/MMC inhibited decrease of the body weight and organ weight in mice intoxificated by CDDP/MMC. The increase of serum blood urea and serum creatinine levels in rats intoxicated by CDDP were significantly inhibited by the co-administrationin with VAWE and CDDP. The decrease of RBC and WBC in rats intoxificated by MMC were significantly inhibited by the co-administration with VAWE and MMC. These results suggest that the combined usage of VAWE and CDDP/MMC drugs may be a new method for prevented or minimized the toxicity of them.

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Cellular internalization effect of Ara27 in various cell lines

  • Minseo Kim;Sangkyu Park;Jeongmin Seo;Sangho Roh
    • 한국동물생명공학회지
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    • 제37권4호
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    • pp.239-245
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    • 2022
  • Protein and peptide candidates are screened to apply therapeutic application as a drug. Ensuring that these candidates are delivered and maximized effectiveness is still challenging and a variety of studies are ongoing. As drug delivery system vehicles, cell-penetrating peptide (CPP) can deliver various kinds of cargo into the cell cytosol. In a previous study, we developed Ara27 CPP, which are a zinc knuckle family protein of Arabidopsis, and confirmed internalization in human dermal fibroblasts and human dental pulp stem cells at low concentration with short time treatment condition without any toxicity. Ara27, an amphipathic CPP, could be modified and utilized in the biomedical field excluding the risk of toxicity. Therefore, we would like to confirm the non-toxic induced penetrating ability of Ara27 in various cell lines. The purpose of this study was to screen the cell internalization ability of Ara27 in various cell lines and to confirm Ara27 as a promising core CPP structure. First, Ara27 was screened to confirm non-toxicity concentration. Then, fluorescence-labeled Ara27 was treated on human normal cell lines, cancer cell lines and animal cell lines to identify the cellular internalization of Ara27. Ara27 was well intracellular localized in all cell lines and the intensity of fluorescence was remarkably increased in time pass manner. These results indicate that Ara27 has the potential as a core structure for applications in various drug delivery systems.

Dextran-Phthalylsulfathiazole의 합성과 항균성 (Synthesis and Antibiotic activity of Dextran-Phthalysulfathiazole)

  • 김판기;이기창;황성규;오세영
    • 한국식품위생안전성학회지
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    • 제12권3호
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    • pp.228-233
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    • 1997
  • Drug Dclivcry system (DDS) purpose to getting better remedial result by improving medication from ordinary methods. Applied for DDS, to improve selectivity and comtinuity during absorbing and delivery step, polmer drug (prodrug) was prepared by the esterification with dextran in such of biodegradable polymer and phthalylsulfathiazole with is efficient for entilitis. The polymer durg was prepared with dextran and phthalylsulfathiazole by the esterification. The synthetic procedures of polymer drug was performed by acid chloride and DCC methods. Polymer drug was synthesized in high yield by acid chloride method than DCC method. The antibiotic activities of polymer drug exhibited growth-inhibitory activity against Staphylococcus aureus, Staphylococcus epidermidis, E. coli, Salmonella typhimurium, Klebsiella pneumoniae at the concentration of 500 *g/m* in general through in vitro. As a result of test, polymer drug has 1/2 MIC than phthalylsulfathiazole. Also, it has high level MIC as much as phthalylsulfathiazole with Proteus, Pseudomonas. We conducted possibility of DDS as an applied for medicine with synthesized polymer drug by using natrural polymer. We consider that clinical research must be followed to verify safety and efficacy for controlled release, activity and toxicity.

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Effects of Extended Storage of Chlorhexidine Gluconate and Benzalkonium Chloride Solutions on the Viability of Burkholderia cenocepacia

  • Ahn, Youngbeom;Kim, Jeong Myeong;Lee, Yong-Jin;LiPuma, John J.;Hussong, David;Marasa, Bernard S.;Cerniglia, Carl E.
    • Journal of Microbiology and Biotechnology
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    • 제27권12호
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    • pp.2211-2220
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    • 2017
  • Chlorhexidine gluconate (CHX) and benzalkonium chloride (BZK) formulations are frequently used as antiseptics in healthcare and consumer products. Burkholderia cepacia complex (BCC) contamination of pharmaceutical products could be due to the use of contaminated water in the manufacturing process, over-diluted antiseptic solutions in the product, and the use of outdated products, which in turn reduces the antimicrobial activity of CHX and BZK. To establish a "afe use" period following opening containers of CHX and BZK, we measured the antimicrobial effects of CHX ($2-10{\mu}g/ml$) and BZK ($10-50{\mu}g/ml$) at sublethal concentrations on six strains of Burkholderia cenocepacia using chemical and microbiological assays. CHX (2, 4, and $10{\mu}g/ml$) and BZK (10, 20, and $50{\mu}g/ml$) stored for 42 days at $23^{\circ}C$ showed almost the same concentration and toxicity compared with freshly prepared CHX and BZK on B. cenocepacia strains. When $5{\mu}g/ml$ CHX and $20{\mu}g/ml$ BZK were spiked to six B. cenocepacia strains with different inoculum sizes ($10^0-10^5CFU/ml$), their toxic effects were not changed for 28 days. B. cenocepacia strains in diluted CHX and BZK were detectable at concentrations up to $10^2CFU/ml$ after incubation for 28 days at $23^{\circ}C$. Although abiotic and biotic changes in the toxicity of both antiseptics were not observed, our results indicate that B. cenocepacia strains could remain viable in CHX and BZK for 28 days, which in turn, indicates the importance of control measures to monitor BCC contamination in pharmaceutical products.