• Title/Summary/Keyword: repeated dose

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Controlled Transdermal Delivery of Loxoprofen from an Ethylene-Vinyl Acetate Matrix

  • Ryu, Sang-Rok;Shin, Sang-Chul
    • Journal of Pharmaceutical Investigation
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    • v.41 no.6
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    • pp.347-354
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    • 2011
  • Repeated oral administration of loxoprofen can induce many side effects such as gastric disturbances and acidosis. Therefore, we considered alternative routes of administration for loxoprofen to avoid such adverse effects. The aim of this study was to develop an ethylene-vinyl acetate (EVA) matrix system containing a permeation enhancer for enhanced transdermal delivery of loxoprofen. The EVA matrix containing loxoprofen was fabricated and the effects of drug concentration, temperature, enhancer and plasticizer on drug release were studied from the loxoprofen-EVA matrix. The solubility of loxoprofen was highest at 40% (v/v) PEG 400. The release rate of drug from drug-EVA matrix increased with increased loading dose and temperature. The release rate was proportional to the square root of loading dose. The activation energy (Ea), which was measured from the slope of log P versus 1000/T, was 5.67 kcal/mol for a 2.0% loaded drug dose from the EVA matrix. Among the plasticizer used, diethyl phthalate showed the highest release rate of loxoprofen. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancing effect. In conclusion, for the enhanced controlled transdermal delivery of loxoprofen, the application of the EVA matrix containing plasticizer and penetration enhancer could be useful in the development of a controlled drug delivery system.

Low-Dose Gamma Irradiation as Means of Isolating Carotenoid-Hyperproducing Yeast Mutant

  • Sun, Nam-Kyu;Lee, Seung-Hee;Ahn, Gil-Hwan;Won, Mi-Sun;Song, Kyung-Bin
    • Journal of Microbiology and Biotechnology
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    • v.12 no.6
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    • pp.1010-1012
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    • 2002
  • In order to isolate carotenoid-hyperproducing yeast, low-dose gamma irradiation was used as means of mutagenesis. Phaffia rhodozyma was treated by gamma irradiation of less than 10 kGy, which is considered to be a wholesome irradiation condition established by the Food and Drug Administration. Through repeated rounds of gamma irradiation and visual screening, mutant 3A4-8 was obtained. It produced a $3,824{\mu}g$ carotenoid/g yeast, 69% higher content than $2,265{\mu}g/g$ yeast of the unirradiated one. This result indicates that low-dose gamma irradiation could be used as means of mutagenesis to obtain carotenoid-hyperproducing strain of Phaffia rhodozyma, since only carotenoid-hyperproducing yeast survived gamma irradiation by scavenging oxygen radicals generated by radiolysis of water.

Basic Measurements and Dosage Compensation for Total Body Irradiation (전신조사를 위한 선량 측정과 보상)

  • 김진기;권형철;김정수;김부길;추성실
    • Progress in Medical Physics
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    • v.3 no.1
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    • pp.25-34
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    • 1992
  • For the TBI with medical linear accelerator(6.10MV), we measured basic data for dosage calculation and designed compensation filters to improve dose uniformity. At the distance of 3.4cm from the source, using the specially designed compensation filters reduced with in ${\pm}$5% for mid-depth dose in the phantom seated with flexion of the legs in the field sige up to 120${\times}$120cm$^2$ for the whole body. In repeated measurements for the dose distribution with humanoid phantom contained paraflin compound, measurement error using the TLD chips were less than ${\pm}$5%.

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A 28 Day Repeated Dose-Oral Toxicity Studies of Arisaema Rhizome Aqueous Extracts in Sprague-Dawley Rats (천남성 추출물의 Sprague-Dawley 랫드를 이용한 28일 반복 경구투여 DRF독성시험)

  • Kim, Min-Kyeoung;Lee, Ji Sun;Park, Yeong Chul;Choi, Sun Mi;Lee, Sanghun
    • Korean Journal of Plant Resources
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    • v.28 no.4
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    • pp.371-381
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    • 2015
  • The object of this study was to obtain single oral dose toxicity of Arisaema Rhizome (Arisaema amurense f. serratum (Nakai) Kitag) aqueous extracts. Arisaema Rhizome (Chunnamsong in Korean) is one of the most important folk remedy plants used in Asia. In the study, a 28-day rat oral gavage study has been conducted with the extracts from Arisaema Rhizome at dose of 1,250, 2,500 and 5,000 ㎎/㎏/day. The following endpoints were evaluated: clinical observations, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it was estimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female rats are 5000 ㎎/㎏/day of the water-extracts from Arisaema Rhizome.

Tissue Distribution of Tropane Alkaloids in Rats and its Determination by GC/MS After the Oral Administration of Scopolia Rhizome (GC/MS에 의한 tropane alkaloids의 분석 및 흰쥐의 생체내 분포)

  • 임미애;백승경;이주선;박세연
    • YAKHAK HOEJI
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    • v.43 no.6
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    • pp.729-735
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    • 1999
  • Scopolia rhizome is mistaken as an atractylodes rhizome because of their similarities in shape. That is why atractylodes rhizome imported from China sometimes contain scopolia rhizome, which is very toxic. 8 persons were intoxicated atractylodes after taking imported atractylodes rhizome which is tainted. In kampo medicine prepared with such imported atractylodes rhizome, the level of tropane alkaloids ranged from 1.12∼4.34 mg/dose. In this study, we tried to investigate the tissue distribution of scopolia rhizome in rats. The extracts of scopolia was administered orally to rats (a single dose of 10mg/kg, 20mg/kg and 7 days repeated dose of 10mg/kg). Their blood was collected at 0.5, 1, 2, 4, 6 hrs, and liver, kidney, lung and spleen were collected after 6 hrs. The tissue homogenate was applied to solid phase extraction column for the determination of tropane alkaloids. After the oral administration of 20mg/kg scopolia extracts, l-hyoscyamine was detected in rat blood to 2 hrs after dosing. The concentration of tropane alkaloids was the highest in liver followed by lung, kidney and spleen. However, lung, kidney and spleen were similar in amount.

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High Dose Rate Ir-192 Source Calibration Method with Newly Designed Calibration Jig (고선량 Ir-192선원 교정기의 제작 및 특성)

  • Yi, Byong-Yong;Choi, Eun-Kyung;Chang, Hye-Sook
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.299-303
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    • 1989
  • Authors have developed highly reproducible calibration method for the Micro-Selectron HDR Ir-192 system (Nucletron, Motherland). The new jig has a 10cm radius circular hole in the $30cm{\times}30cm{\times}0.2cm$ acrylic plate, and 5F flexible bronchial tubes are attached around the hole. The source moves along the circle in the tubes and the ionization chamber is placed verticaly at the center of the circular hole (center of the jig). Dose distribution near the center was derived theoretically, and measured with the film dosimetry system. Theoretical calculation and measurement show the error margin below $0.1\%$ for 1mm or 2mm position deviation. We have measured at 12 and 24 points of circle with 1, 6, 11 and 21 second dwell time of source in order to calculate the activity of the source. Measurements have been repeated daily for 50 days. The accuracy and the reproducibility are below $1\%$ error margin. The half life of the source from our measurement is estimated $73.4\pm0.4$ days.

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Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (2) - Oral Combination Treatment of Tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day Repeated Pretreated Rats with 8-day Repeated Co-administration -

  • Park, Soo Jin;Kwak, Min A;Park, Sung Hwan;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.20 no.2
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    • pp.97-109
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    • 2016
  • Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

Absorbed and effective dose from spiral and computed tomography for the dental implant planning (치과 임프란트 치료 계획을 위한 나선형 일반 단층촬영과 전산화 단층촬영시 흡수선량 및 유효선량 평가)

  • Hong Beong-Hee;Han Won-Jeong;Kim Eun-Kyung
    • Imaging Science in Dentistry
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    • v.31 no.3
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    • pp.165-173
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    • 2001
  • Objectives : To evaluate the absorbed and effective doses of spiral and computed tomography for the dental implant planning. Materials and Methods: For radiographic projection, TLD chips were placed in 22 sites of humanoid phantom to record the exposure to skin and the mean absorbed dose to bone marrow, thyroid, pituitary, parotid and submandibular glands and nesophagus. Effective dose was calculated, using the method suggested by Frederiksen et al.. Patient situations of a single tooth gap in upper and lower midline region, edentulous maxilla and mandible were simulated for spiral tomography. 35 axial slices (maxilla) and 40 axial slices (mandible) with low and standard dose setting were used for computed tomography. All the radiographic procedures were repeated three times. Results: The mean effective dose in case of maxilla was 0.865 mSv, 0.452 mSv, 0.136 mSv and 0.025 mSv, in spiral tomography of complete edentulous maxilla, computed tomography with standard mAs, computed tomography with low mAs and spiral tomography of a single tooth gap (p<0.05). That in case of mandible was 0.614 mSv, 0.448 mSv, 0.137 mSv and 0.036 mSv, in spiral tomography of complete edentulous mandible, computed tomography with standard mAs, computed tomography with low mAs and spiral tomography of a single tooth gap (p<0.05). Conclusions: Based on these results, it can be concluded that low mAs computed tomography is recommended instead of spiral tomography for the complete edentulous maxilla and mandible dental implant treatment planning.

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Behavioral and Physiological Effects Induced by the Acute Administration of Melatonin in Healthy Young Men (정상인에서의 멜라토닌 투여에 따른 행동 및 생리적 효과)

  • Joe, Sook-Haeng;Nam, Min
    • Korean Journal of Psychosomatic Medicine
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    • v.5 no.2
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    • pp.195-204
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    • 1997
  • Objectives : The behavioral and physiological effects following low doses and high doses of melatonin have not been fully explored. In this study the authors investigated the nature and extent of the hypnotic effects, oral temperature, blood pressure effects, performance effects and subjective feelings following the acute administration of low pharmacological oral doses of melatonin at mid-day. Methods : Thirty-five healthy young medical students were randomly assigned to receive 6mg of oral melatonin(N=11), 12mg of oral melatonin(N=12) or a placebo(N=12) in a double-blind, placebo controlled trial. Measures of the behavioral and physiological effects used in the study were Stanford Sleepiness Scale, Digit Symbol Substitution Test, Trail test and visual analogue scale for subjective feelings. Oral temperature and blood pressure were measured. The subjects were studied between 10:00 and 16:00 hours. Data were analyzed by using repeated-measures analyses of variance(ANOVA). Results: Melatonin produced statistically significant effects on oral temperature, but there were no significant effects on time and the $dose{\times}time$ interaction. There was a significant difference on oral temperature between the 12mg oral melatonin group and the placebo group at 12:00 and 16:00 hours, but no significant difference between the 12mg and the 6mg oral melatonin groups. Melatonin produced a dose-related increase in subjective sleepiness and had significant effects on time, the $dose{\times}time$ interaction. There was a significant difference on subjective sleepiness among the placebo, 6mg, 12mg oral melatonin groups at 13:00-16:00 hours. Melatonin did not produce statistically significant dose-related effects on subjective fatigue but produced significant effects on time and the $dose{\times}time$ interaction. There was a significant difference on subjective fatigue between the 12mg, the 6mg oral melatonin groups and the placebo group at 13:00 hour. Conclusions : These data indicated that acute administration of melatonin at mid-day increased subjective sleepiness and fatigue but decreased oral temperatures. These effects were shown especially in 12mg oral melatonin group.

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Repeated-Dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

  • Jang, Jongwon;Seo, Wookcheol;Chu, Hongmin;Park, Kyungtae;Kim, SunKyung;Park, Ju-Hun;Shin, Joon young;Choi, Dong ho;Kang, Hyung Won;Kim, Sungchul
    • Journal of Acupuncture Research
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    • v.37 no.2
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    • pp.110-117
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    • 2020
  • Background: The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP). Methods: A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a med-dose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene's test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group. Results: During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls. Conclusion: No toxicological changes related to the administration of test substances were observed. Therefore, the LD50 (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.