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Effects of the mixed formulation of sorafenib and blue honeysuckle on the pharmacokinetics profiles of sorafenib

  • Kang, Hyun-Gu;Kang, Su-Jin;Ku, Sae-Kwang;Choi, Seong-Hun;Lee, Young-Joon
    • Journal of Society of Preventive Korean Medicine
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    • v.23 no.1
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    • pp.83-94
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    • 2019
  • Objective : This study investigated the effects of concentrated and lyophilized blue honeysuckle powders (BH) on the pharmacokinetics (PK) of sorafenib were observed. Method : The blood was collected at 0.5 hr before single oral treatment of sorafenib (40 mg/kg) or sorafenib with BH (400, 200 and 100 mg/kg) mixed formulas administration, and 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs after the end of single or mixed formula administration. Plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$ of sorafenib were analysis as compared with sorafenib single treatment. Results : Single oral administration of mixed formulas induced significant increases of plasma sorafenib concentrations from 0.5 hr after end of administration throughout all blood collected time points, as compared with sorafenib single formula treated rats, and significant decreases of sorafenib Tmax with increases of Cmax, $AUC_{0-t}$ and $AUC_{0-inf}$ were detected in sorafenib and BH 400 mg/kg mixed formulation treated rats as compared with sorafenib single formula treated rats, respectively. Inaddition, sorafenib and BH 200 or 100 mg/kg mixed formula treated rats also showed significant increases of sorafenib Cmax, $AUC_{0-t}$ and $AUC_{0-inf}$, respectively. Conclusions : According to these results, mixed formulation of BH with sorafenib increased the bioavailability of sorafenib through the increment of the absorptions.

Micronucleus Test of DHU001, a Polyherbal Formula, in Bone Marrow Cells of Male ICR Mice

  • Roh, Seong-Soo;Lee, Hyeung-Sik;Ku, Sae-Kwang
    • Toxicological Research
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    • v.25 no.4
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    • pp.225-230
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    • 2009
  • The genotoxic effects of DHU001, a polyherbal formula were evaluated using the mouse micronucleus test. DHU001 was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppression. The results indicats that DHU001 showed no genotoxicity effects up to 2000 mg/kg dosing levels and did not influenced on the total white blood cells and differential counts. In addition, it is also considered that there were no problems from cytotoxicity of DHU001 tested in this study because the polychromatic erythrocyte ratio was detected as > 0.41 in all tested groups.

Single Oral Dose Toxicity Evaluation of Samul-tang, a Traditional Herbal Formula, in Crl:CD (SD) Rats

  • Yoo, Sae-Rom;Jeong, Soo-Jin;Shin, Hyeun-Kyoo
    • The Journal of Korean Medicine
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    • v.35 no.2
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    • pp.28-33
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    • 2014
  • Background: Samul-tang (Si-Wu-Tang, SMT) is a traditional herbal formula, which has been widely used to treat various diseases such as menstrual irregularity, bleeding and leucorrhea. Although many studies have investigated the pharmacological properties of SMT, its toxicity information has not yet been fully elucidated. Methods: Five Sprague Dawley (SD) rats of each sex were given a single dose (5000 mg/kg) of SMT by gavage; control rats received the vehicle only. After the single administration, mortality, clinical signs, body weight changes and gross findings were monitored for 15 days in accordance with Good Laboratory Practice (GLP) principles. Results: In a single oral dose toxicity study, there was no adverse effect on mortality, clinical sign, body weight change or gross finding in any treatment group. Conclusions: The results indicate that SMT did not induce toxic effects at a dose level up to 5000 mg/kg in rats and its median lethal dose ($LD_{50}$) was considered to be over 5000 mg/kg/day body weight for both genders.

Micronucleus Test of Kong-Jin-Dan, a Polyherbal Formula, in Bone Marrow Cells of Male ICR Mice

  • Lee, Sang-Nam;Park, Ji-Ha;Ku, Sae-Kwang
    • Toxicological Research
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    • v.24 no.3
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    • pp.213-218
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    • 2008
  • In this research, the genotoxic effects of Kong-Jin-Dan(KJD), a polyherbal formula were evaluated using the mouse micronucleus test. KJD was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppress. The results obtained indicated that KJD shows no genotoxicity effects up to 2000 mg/kg dosing levels, but KJD shows slight increased trends in the blood total leukocyte numbers as pharmacological effects of immune stimulation. In addition, it is also considered that there were no problems from cytotoxicity of KJD tested in this study because the polychromatic erythrocyte ratio was detected as > 0.42 in all tested groups.

Single Oral Dose Toxicity Test of Kong-Jin-Dan, a Polyherbal Formula in ICR Mice

  • Park, Mee-Yeon;Choi, Hae-Yun;Kim, Jong-Dae;Lee, Hyeung-Sik;Ku, Sae-Kwang
    • Biomolecules & Therapeutics
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    • v.15 no.4
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    • pp.245-251
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    • 2007
  • The object of this study was to evaluate the single dose toxicity of Kong-Jin-Dan (KJD), a polyherbal formula in male and female mice. KJD was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for increases of lymphoid organ weights in KJD-dosing groups. These increases of lymphoid organ weights considered that related to the immune modulate effect of KJD not toxicological signs. In addition, no KJD-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the KJD does not cause any toxicological signs. The $LD_{50}$ and approximate LD of KJD extracts in both female and male mice were considered as over 2000 mg/kg.

Effect of DHU001, a Polyherbal Formula on Formalin-induced Paw Chronic Inflammation of Mice

  • Cho, Yoon-Hee;Chung, In-Kwon;Cheon, Woo-Hyun;Lee, Hyeung-Sik;Ku, Sae-Kwang
    • Toxicological Research
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    • v.27 no.2
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    • pp.95-102
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    • 2011
  • The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for various respiratory disorders were evaluated on the formalin-induced paw chronic inflammation in mice after oral administration. Mice were subaponeurotically injected in the left hind paw with 0.02 ml of 3.75% formalin, then subjected to 500, 250 and 125 mg/kg of DHU001 oral administration, once a day for 10 days during which then the hind-paw thickness and volume were measured daily. The paw wet-weight, histological profiles, histomorphometrical analyses and paw tumor necrosis factor (TNF)-${\alpha}$ contents were conducted at termination. After two formalin treatments, a marked increase in the paw thickness and volume was detected in the formalin-injected control as compared with that in the intact control, plus at the time of sacrifice the paw wet-weights, paw TNF-${\alpha}$ contents were also dramatically increased with severe chronic inflammation signs at histopathological observations. However, these formalin-induced chronic inflammatory changes were dramatically decreased by treatment of dexamethasone and all three different dosages of DHU001. DHU001 has favorable effects on formalin-induced chronic inflammation mediated by TNF-${\alpha}$ suppression, and DHU001 may represent an alternative approach for the treatment of chronic inflammatory diseases.

Synergic Effects of Mixed Formula Consisted of Polycan and Calcium-gluconate on the Experimental Periodontitis and Alveolar Bone Loss in Rats

  • Lee, Won-Ho;Kim, Kyung Hu;Kang, Su Jin;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.18 no.1
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    • pp.125-138
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    • 2014
  • Objective : Polycan, exopolymers purified from Aureobasidium pullulans SM-2001 and calcium gluconate have been showed favorable inhibitory effects on the periodontitis and related alveolar bone losses through antioxidant and anti-inflammatory activities, respectively. In the present study, we intended to observe the possible synergic effects of mixed formula consisted of Polycan and calcium gluconate on ligation-induced experimental periodontitis and related alveolar bone losses in rats, and to select the fittest compositions for further developing as effective agents to ameliorate periodontal diseases. Method : Experiments were conducted as two separated two tests - first is synergic effects of Polycan and calcium gluconate 1:1, 1:9 and 9:1 mixtures, and second is 1:99, 2:98, 4:96, 8:92 and 1:9 mixtures. Experimental periodontal diseases were induced by ligature placed around the cervix of upper left incisior teeth of rats. One day after ligation placements, 200mg/kg of each single or mixed formulas of Polycan or/and calcium gluconate were orally administered for 10 days. The changes on the alveolar bone loss index and maxillary bone mineral density (BMD) were observed for detecting alveolar bone losses, and for anti-inflammatory effects, myeloperoxidase (MPO) activities and proinflammatory cytokine (tumor necrosis factor; TNF-${\alpha}$) contents were also evaluated in gingival tissues around ligature placed incisior teeth. The results of mixtures were compared with those of singe Polycan and calcium gluconate treated rat. Results : Each single or mixed formulas of Polycan or/and calcium gluconate favorably and significantly inhibited the inflammatory changes. The inhibitory effects of mixed formula consisted of Polycan and calcium gluconate 1:9 showed against periodontitis and related alveolar bone losses as compared with those of each Polycan and calcium gluconate single formula (p<0.05). In second experiment, Polycan and calcium gluconate 2:98, 4:96, 8:92 and 1:9 mixed formulas also showed significant increased anti-inflammatory and inhibitory effects against alveolar bone losses as compared with those of each single formula. Among them, Polycan and calcium gluconate 2:98 showed the highest efficacy against to ligation-induced experimental periodontitis and related alveolar bone losses. Conclusion : The results obtained in this study suggest that appropriated mixtures of Polycan and calcium gluconate showed synergic inhibitory effects against ligation-induced experimental periodontitis and related alveolar bone losses in rats. Moreover, Polycan and calcium gluconate 2:98 showed the highest efficacies in this experiment, suggesting the fittest composition for further developing as effective agents to ameliorate periodontal diseases.

Development of the Technical Calculation System for Transmission Line in Myanmar (미얀마 송전선로 설계 기술계산시스템 개발)

  • Baik, Seung-Do;Min, Byeong-Wook;Kim, Jong-Hwa;Shin, Tai-Woo;Kim, Sae-Hyun;Park, Jae-Ung
    • Proceedings of the KIEE Conference
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    • 2005.07a
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    • pp.632-634
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    • 2005
  • Korea takes part in overseas business by use of accumulated advanced technology through construction of the worlds first 765kV double circuit transmission system designed with pure local technology. 'Development Study on the Power System Network Analysis in Myanmar' was received in the year 2001 and was completed in the year 2002. The following project,'Feasibility Study and Basic Designs for the 500kV Transmission System in Myanmar' has been in progress since January, 2004. With regards to this project the master plan for the Myanmar long term power system was submitted in January 2005, and now the basic designs for the 500kV transmission system construction are in progress. Technical data for the design of the transmission line is calculated using a very complex numerical formula that is almost impossible to be completed by hand. So the transmission technical calculation system was developed to calculate and support Myanmar technical data for the design of transmission line with respect to factors such as wind prossure load, tower design data conductor design data and insulator design data on the basis of weather conditions for the Myamar transmission line design area of the Myanmar 500kV trans- mission line construction basic design.

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A Study of the Voltage drops computation program on multi-distributed random loads (다중 분산부하 전압강하산정 프로그램 연구)

  • Kang, Cha-Nyeong;Kwon, Sae-Hyuk;Cho, Sung-Pil
    • Proceedings of the Korean Institute of IIIuminating and Electrical Installation Engineers Conference
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    • 2006.05a
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    • pp.37-42
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    • 2006
  • The voltage drop in electrical circuits causes a heat accumulation of wiring. This heat could change the specific character of an insulator and deteriorate the dielectric strength so that it could affect an electric leakage, an electric ant a power failure and a fire caused by the short circuit. Therefore optimal design for voltage drop in electrical wiring became an important factor to ensure the safety and economical efficiency of electrical facilities. So in this paper, I analyzed consequences that voltage drop affects in electrical wiring in multi-distributed system used for low electrical system such as road lights, Building, subway station which needs securities for the public society. And I proposed voltage drops computation program and optimal design to ensure the safety and economical efficiency.

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Development of the Technical Calculation System for Transmission Line (송전선로 설계 기술자료 계산시스템 개발)

  • Byun Gang;Min Byeong Wook;Wi Hwa Bog;Kim Sae Hyun;Park Kee Yong;Namkung Do
    • Proceedings of the KIEE Conference
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    • summer
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    • pp.488-490
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    • 2004
  • The technical data for transmission line design and maintenance are calculated by a very complicated numerical formula so it is almost impossible to solve them by hand. Therefore the TOWER+ EXPERT SYSTEM was developed to systematically support technical data for transmission line design and maintenance. This system is able to calculate technical data which is applied to all conductors in our county, - that is 12 kinds of systems with 86 numbers of standard conductors, - and is programed to be user friendly by adopting dialogue windows, menu selection functions. Moreover, it minimizes input data by automatically providing standard transmission line design data, and it includes guidance of applicable work, program usage, data input process, help, explanation of terms and automatic error recovery functions that even a beginner can easily use.

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