• Title/Summary/Keyword: Drug Toxicity

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Drug Release and Skin Irritancy of Poloxamer Gel Containing Kojic Acid (코지산을 함유한 폴록사머 겔 제제의 약물방출 및 피부자극성)

  • Park, Eun-Woo;Cho, Seong-Wan;Kim, Dong-Sup;Choi, Ki-Hwan;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.28 no.3
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    • pp.177-183
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    • 1998
  • Low toxicity, reverse thermal gelation and high drug loading capabilities suggest that poloxamer 407 gels have great potential as a topical drug delivery system. Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of skin irritancy due to its acidic pH. Poloxamer gels of different polymer contents were formulated to overcome the problem and compared to the cream type formulations of either w/o/w multiple emulsion cream or o/w type emulsion cream. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solutions. Drug release from w/o/w multiple emulsion cream was controlled by oil membrane, showing the apparent zero order release kinetics. The KA release from the poloxamer gels was also controlled by the gel matrix, showing that drug release increased linearly as KA contents increase, but decreased exponentially as the polymer contents increase. In the skin irritancy test, the primary irritancy index(PII) of poloxamer gel base was lower than those of multiple emulsion cream base and o/w cream. Depending on KA contents or polymer contents in the gel. PH values in poloxamer gels were ranged from 1.3 to 2.0, which are interpreted as low or negligible irritation on skin. There was a good correlation between the log value of flux in drug release and PII value in skin irritation. It was possible to conclude that the poloxamer gels containing KA might be a good candidate for an antimelanogenic topical delivery system by virtue of the controlled release of the drug and the reduced skin irritancy.

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Synthesis and Characterization of the Tumor Targeting Mitoxantrone-Insulin Conjugate

  • Liu, Wen-Sheng;Yuan-Huang;Zhang, Zhi-Rong
    • Archives of Pharmacal Research
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    • v.26 no.11
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    • pp.892-897
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    • 2003
  • Anticancer drugs have serious side effects arising from their poor malignant cells selectivity, Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at $37^{\circ}C$ within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1 % of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 $\mu g \cdot$ h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 1l9 h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes ($TI^c$) no larger than 0.3 besides good tumor targeting efficiency with $TI^c$ of 1.67. The results suggest the feasibility to promote the curative effect in ca.ncer chemotherapy by using insulin as the vector of anti-cancer drugs.

Analysis Method Development for Bound-MCPD (3-MCPD 지방산에스테르 분석법)

  • Woo, Sung-Min;Oh, Jae-Ho;Jang, Young-Mi;Kim, Mee-Hye
    • Journal of Food Hygiene and Safety
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    • v.25 no.4
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    • pp.294-302
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    • 2010
  • Toxicity of 3-MCPD that comes from food manufacture and processing is well-known. Recent studies reported that 3-MCPD fatty acid ester which is formed by metabolic material was 10~2000 times as much as 3-MCPD in food. This study made analysis method of 3-MCPD fatty acid esters by recent research and laboratory work, and determined the content of 3-MCPD and 3-MCPD fatty acid esters in sources and meat processing products. 3-MCPD fatty acid esters were analysed by GC/MS, which were hydrolyzed from fatty acid and then transferred 3-MCPD was extracted and reacted with derivative subject. As a result of analysis method validation, LOD was 5.4ppb, LOQ was 9.0ppb.

Acute Toxicity of Kami-Okchun-San in ICR-Mice (가미옥천산의 ICR 마우스 경구 투여에 의한 급성 독성시험 연구)

  • Ko Byoung-Seob;Park Min-Jung;Park So-Min;Jeon Won-Kyung;Chun Jin-Mi;Joung Pil-Mun;Park Sun-Min;Choi Soo-Bong;Oh Myung-Sook;Chang Mun-Seog;Park Seong-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.5
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    • pp.1200-1203
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    • 2005
  • Kami-Okchun-San(OCS) is known as an effective herbal medicine on Type 2 diabetes. We peformed to investigate acute toxicity of OCS on ICR mice. ICR mice in acute toxicity experiment were administered orally with dosages of 3,200mg/kg (low dosage group), 4,000mg/kg (middle dosage group), 5,000mg/kg (high dosage group) per single time, respectively. Body weights, clinical signs, motalities and histopathological finding were observed daily for 14 days according to the Regulation of Korean Food and Drug Administration(1999. 12. 22). Single oral administration of OCS with different dosages, no animals died of the test drug. Autopsy of animal revealed no abnormal gross findings. Therefore, LD50 value of OCS for ICR mice was more than 5,000mg/kg on oral route. Normally increasing changes were observed in body weight, drinking water and food intake in every dosage group. Hematological parameters were also observed normally in all animals. No histopathological lesions were observed in both control and treated animals. Above data suggest that no toxic dose level of OCS in ICR mice is considered to be more than 5,000mg/kg. Therefore, it was concluded that OCS have no effect on acute toxicity and side effect in ICR mice.

Gene Medicine : A New Field of Molecular Medicine

  • Kim, Chong-Kook;Haider, Kh-H;Lim, Soo-Jeong
    • Archives of Pharmacal Research
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    • v.24 no.1
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    • pp.1-15
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    • 2001
  • Gene therapy has emerged as a new concept of therapeutic strategies to treat diseases which do not respond to the conventional therapies. The principle of gene therapy is to Introduce genetic materials into patient cells to produce therapeutic proteins in these cells. Gene therapy is now at the stage where a number of clinical trials have been carried out to patients with gene-deficiency disease or cancer. Genetic materials for gene therapy are generally composed of gene expression system and gene delivery system. For the clinical application of gene therapy in a way which conventional drugs are used, researches have been focused on the design of gene delivery system which can offer high transfection efficiency with minimal toxicity. Currently, viral delivery systems generally provide higher transfection efficiency compared with non-viral delivery systems while non-viral delivery systems are less toxic, less immunogenic and manufacturable in large scale compared with viral systems. Recently, novel strategies towards the design of new non-viral delivery system, combination of viral and non-viral delivery systems and targeted delivery system have been extensively studied. The continued effort in this area will lead us to develop gene medicine as "gene as a drug" in the near future.

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Analysis and Stability Test of the Extracts from Epimedii Herba, Atractylodis Rhizoma Alba and Polygalae Radix for Toxicity Study (음양곽, 백출 및 원지의 독성평가를 위한 성분분석 및 안정성 시험)

  • Keum, Jeong Ho;Han, Hyoung Yun;Seok, Ji-Hyeon;Roh, Hang Sik;Lee, Jong-Kwon;Jeong, Ja Young;Kim, Jeong Ah;Woo, Mi Hee;Choi, Jae Sue;Min, Byung Sun
    • Korean Journal of Pharmacognosy
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    • v.45 no.2
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    • pp.135-140
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    • 2014
  • A simple and reliable reverse phase HPLC method was developed to determine pharmacologically active marker compounds of Epimedii Herba, Atractylodis Rhizoma Alba, and Polygalae Radix. The stability test of water-extracts of the three natural medicines has been evaluated for six months. However, no significant changes in the content of the marker compounds of each extract were observed during the time of investigation.

One Case of Drug-Induced Liver Injury Treated with Saenggangeonbi-tang (생간건비탕(生肝健脾湯)을 이용한 급성 약인성 간손상 치험 1례)

  • Jeong, Tae-Young;Choi, Hong-Sik
    • The Journal of Internal Korean Medicine
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    • v.25 no.4
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    • pp.207-211
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    • 2004
  • Recently a case of liver injury from ingestion of Taeyeumjowi-tang containing Ma-huang(Ephedra sinica stapf) arose. The patient, a 30 year-old woman, was diagnosed with asthenia and anorexia after 6 weeks of ingesting Taeyeumjowi-tang containing Ma-huang(Ephedra sinica stapf) as a treatment for her obesity. Tests showed elevated levels of serum transaminase(ALT 903 IU/L, AST 716 IU/L), alkaline phosphatase (229 IU/L), total bilirubin (1.4 mg/dl). Other possible causes of liver injury were excluded by laboratory test and medical history, so the liver injury was taken to be drug-induced. Saenggangeonbi-tang was administered. After 2 weeks of treatment with this medication, the clinical symptoms and liver function improved. This case is reported with a call for further accumulation of objective data on drug-induced liver injury, and to bring more attention to the relative levels of safety and toxicity of herbal medicines.

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Covalent Immobilization of Trypsin on a Novel Aldehyde-Terminated PAMAM Dendrimer

  • Hamidi, Aliasghar;Rashidi, Mohammad R.;Asgari, Davoud;Aghanejad, Ayuob;Davaran, Soodabeh
    • Bulletin of the Korean Chemical Society
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    • v.33 no.7
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    • pp.2181-2186
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    • 2012
  • Dendrimers are a novel class of nonlinear polymers and due to their extensive applications in different fields, called versatile polymers. Polyamidoamine (PAMAM) dendrimers are one of the most important dendrimers that have many applications in nanobiotechnology and industry. Generally aldehyde terminated dendrimers are prepared by activation of amine terminated dendrimers by glutaraldehyde which has two problems, toxicity and possibility of crosslink formation. In this study, novel aldehyde-terminated PAMAM dendrimer was prepared and used for covalent immobilization of trypsin by the aim of finding a special reagent which can prevent crosslinking and deactivation of the enzyme. For this purpose aminoacetaldehydedimethylacetal (AADA) was used as spacer group between aldehyde-terminated PAMAM and trypsin.The findings of this study showed that immobilization of trypsin not only resulted higher optimal temperature, but also increased the thermal stability of the immobilized enzyme in comparison to the free enzyme.

Neurotoxicity of Synthetic Cannabinoids JWH-081 and JWH-210

  • Cha, Hye Jin;Seong, Yeon-Hee;Song, Min-Ji;Jeong, Ho-Sang;Shin, Jisoon;Yun, Jaesuk;Han, Kyoungmoon;Kim, Young-Hoon;Kang, Hoil;Kim, Hyoung Soo
    • Biomolecules & Therapeutics
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    • v.23 no.6
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    • pp.597-603
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    • 2015
  • Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

A Literatural Reserch for the Practical Use of the Balsaminaceae (봉선화과 식물의 활용을 위한 문헌적 조사)

  • Bang, Jeong Hwan;Chong, Myong Soo
    • Journal of Korean Medical Ki-Gong Academy
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    • v.13 no.1
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    • pp.77-104
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    • 2013
  • In this study we examined the concerned literature for clinical use of Balsaminaceae plants focusing on the latest literature "zhong hua ben cao"(chinese materia medica, 1998). The findings were summarized as follows: 1. As an original plant, 27 species have been reviewed. 2. As a result of investigating oriental drug names by medicinal using part, a survey reported that the total of 22 species of oriental drug names, including 14 species of herba, 3 species of flos, 4 species of radix and rhizoma, and 1 species of semen, are being used for clinical use. 3. When we examined oriental drugs with five flavors by calculating and arranging their nature, effect, toxicity with points for conveniences sake, pungent and bitte showed 13 points, respectively, as main flavors. In drug nature, warm property of drug indicated 10 points and cold property of drug obtained 6 points. But as for other oriental drug, it is thought that we can recognize their significance. 4. With respect to efficacy, activating blood drug reached 10 kinds and wind- damp-dispelling 7 kinds, according to the examination. 5. In the examination on components and medicinal action, we examined that components are recorded in only impatiens balsamina's whole grass, flowers, root, root stems, and seeds, and Impatiens noli-tangere's whole grass. In medical action, we found out that the components are recorded in impatiens balsamina' flowers and seeds; impatiens noli-tangere's whole grass and flowers; and Impatiens textori' whole grass. 6. As a result of examining clinical prescription, the total of 84 kinds of clinical prescriptions by disease nature were examined, of which the prescription of Impatiens balsamina showed 19 cases in total, which was remarkable.