• Title/Summary/Keyword: Drug Distribution

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The Functional Role of Lysosomes as Drug Resistance in Cancer (항암제 내성에 대한 라이소좀의 역할)

  • Woo, Seon Min;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.31 no.5
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    • pp.527-535
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    • 2021
  • Lysosomes are organelles surrounded by membranes that contain acid hydrolases; they degrade proteins, macromolecules, and lipids. According to nutrient conditions, lysosomes act as signaling hubs that regulate intracellular signaling pathways and are involved in the homeostasis of cells. Therefore, the lysosomal dysfunction occurs in various diseases, such as lysosomal storage disease, neurodegenerative diseases, and cancers. Multiple forms of stress can increase lysosomal membrane permeabilization (LMP), resulting in the induction of lysosome-mediated cell death through the release of lysosomal enzymes, including cathepsin, into the cytosol. Here we review the molecular mechanisms of LMP-mediated cell death and the enhancement of sensitivity to anticancer drugs. Induction of partial LMP increases apoptosis by releasing some cathepsins, whereas massive LMP and rupture induce non-apoptotic cell death through release of many cathepsins and generation of ROS and iron. Cancer cells have many drug-accumulating lysosomes that are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. Lysosomal sequestration of hydrophobic weak base anticancer drugs can have a significant impact on their subcellular distribution. Lysosome membrane damage by LMP can overcome resistance to anticancer drugs by freeing captured hydrophobic weak base drugs from lysosomes. Therefore, LMP inducers or lysosomotropic agents can regulate lysosomal integrity and are novel strategies for cancer therapy.

Clinical study on Chiropract-Drug treatment, Yongkakkyo-tang which is used for the treatment of arthrosis, vertebra disease (척추 관절 질환 치료에 응용되는 추나.약물요법 중 용각교탕을 중심으로 한 임상적 고찰)

  • Shin, Jun-Sik
    • Korean Journal of Oriental Medicine
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    • v.1 no.1
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    • pp.289-319
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    • 1995
  • The clinical studies were performed on 301 cases who took Yongkakkyo-tang from June 1993 to December 1994 The results were as follows: 1. About 80%(239 cases) patients who took Yongkakkyo-tang were improved. 2. The ratio of male to female patients was 106:133. In the age distribution, it was found that under 20's were 8%(24/301), 30's and 40's were 33%(98/301), and over 50's was 39%(117/301). 3. In the regional distribution, it was found that Cervical region was 22 cases, thoracic region was 12 cases, cervical & lumbar region complex was 50 cases, upper limbs region was 6 cases, lower limbs region was 12 cases, and lumbar region was 153 cases(64%). 4. Among improved cases, the cases treated only with Yongkakkyo-tang were 16(5%), the cases treated with Yongkakkyo-tang, and treated with Chiropractic were 19(6%), the cases treated with Yongkakkyo-tang and Yanggun-tang chiropratic were 133(44%). 5. Among improved cases, the number of Chiropractic treatment, less then 15 teimes were 69 cases, 15 to 30 times were 91cases. Basedon these results, it was shown that Yongkakkyo-tang could be used for the treatment of degenerative disease of vertebra, and the treatment with Yongkakkyo-tang, Yanggun-tang and Chiropratic is more effective.

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Effect of Hepatic Cirrhosis on the Pharmacokinetics of Theophylline in Rats

  • Nam, Bang-Hyun;Sohn, Dong-Hwan;Ko, Geonil;Kim, Jae-Baek
    • Archives of Pharmacal Research
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    • v.20 no.4
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    • pp.318-323
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    • 1997
  • The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethyinitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life $(t_{1/2})$ in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL $(8.67{\pm}4.85%)$ decreased about four-folds, but in DMNA $(73.00{\pm}9.85%)$ similar result war observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.

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Amorphous Ultrafine Particle Preparation for Improvement of Bioabailability of Insolube Drugs: Effect of Co-Grinding of UDCA with SLS (난용성 의약품의 생체이용률 증진을 위한 무정형 초미립자의 조제 : UDCA와 SLS의 혼합분쇄 효과)

  • 정한영;곽성신;김현일;최우식
    • YAKHAK HOEJI
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    • v.46 no.2
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    • pp.102-107
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    • 2002
  • The particle size of medicinal materials is an important physical property which affects the pharmaceutical behaviors such as dissolution, chemical stability, compressibility and bioavailability of solid dosage forms. The size reduction of raw pharmaceutical powder is needed to formulize insoluble drugs or slightly soluble drugs and to improve the pharmaceutical properties such as the solubility, the pharmaceutical mixing and the dispersion. The objective of the present study is to evaluate the grinding characteristics of ursodeoxycholic acid(UDCA) as a model of insoluble drugs. The effects of the grinding time and the amount of additive on particle size distribution of ground UDCA were investigated. Grinding of insoluble drug, UDCA and a series of dry co-grinding experiments of UDCA with sodium lauryl sulfate(SLS) as an additive were carried out using a planetary ball mill. It was measured that the median diameter and the particle size distribution of ground products with grinding UDCA and additive SLS by Mastersizer. As a result of co-grinding of UDCA and SLS, the particle size of co-grinding products was decreased more than single grinding one. However, it was observed that co-grinding products were reaggregated to larger particles after 120 min.

State-of-the-Art of Nanotechnology-based Food Products : Toxicity and Risk Assessment(II) (총설 - 나노기술을 적용한 식품의 독성 및 위해성평가 현황(II))

  • Chun, Hyang-Sook;Chang, Hyun-Joo;Ko, Sang-Hoon;Oh, Il-Ung
    • Bulletin of Food Technology
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    • v.24 no.3
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    • pp.308-324
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    • 2011
  • 나노기술을 식품에 응용하게 되면 영양소의 전달, 식품의 색, 향미, 물성 등이 향상되고 식품 포장재나 분석에 응용하는 경우 저장성 증진이나 시료 전처리 효율 및 기기 감도를 증가시키는 것으로 알려지고 있다. 이러한 장점으로 인해 유기 및 무기 나노입자, 나노섬유, 나노에멀전, 나노크레이 등의 나노물질을 식품첨가물, 건강기능소재, 식품 접촉물질 등으로 응용하는 시도가 식품산업계에서 급속히 확산되고 있다. 나노물질의 사용범위가 다양해질수록 나노물질의 환경 및 인체 노출가능성은 높아지게 된다. 그러나 아직 나노물질의 독성 및 위해성에 대해서는 초기 단계 수준의 연구가 진행되고 있는 정도이다. 또한 나노기술의 위험 평가에 대한 신뢰성이 제고될 수 있도록 나노물질에 대한 유해성 자료의 생산뿐만 아니라 나노물질의 물리화학적 특성과 노출량을 측정할 수 있는 적절한 측정수단이 확립되어야 한다. 나아가 식품에 나노기술의 적용으로 인한 이익은 최대화하고 부작용은 최소화하여 소비자의 건강을 보호하기 위해 식품나노물질의 생산, 가공, 유통, 소비, 폐기 등에 관한 전 생애(lifecycle) 평가 및 관리가 이루어지도록 적절한 제도적 장치가 마련되어야 한다.

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Effect of Sodium Taurodeoxycholate on Biliary Excretion of Amaranth as an Anionic Model Drug in Rats (음이온 모델 화합물 아마란스의 담즙배설에 미치는 타우로데옥시콜레이트의 영향)

  • Shim, Chang-Koo;Chung, Suk-Jae
    • Journal of Pharmaceutical Investigation
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    • v.16 no.3
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    • pp.110-117
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    • 1986
  • Plasma disappearance of amaranth (AM), a model compound of organic anionic drugs, was retarded by intravenous infusion of taurodeoxycholate (TDC), a representative bile acid, in the rat. Biliary excretion accounted for 30-60% of the systemic excretion of AM. AM seemed to be metabolised in the hepatocyte to form a compound that is excreted more rapidly into the bile than AM itself, considering apparent biliary clearance, $CL_{bil}$, is much larger than systemic clearance, $CL_s$. Decrease in $CL_{bil}$ by TDC infusion might be due to elevated plasma level rather than decreased biliary excretion of AM. Decreased distribution or urinary excretion of AM by TDC was supposed to be one of the probable reasons of elevated plasma level. Competitive inhibition between AM and TDC on tissue distribution and urinary excretion might explain the mechanism. The effect of TDC on the $CL_{bil}$ of methylene blue, a cationic dye, was quite different from that of AM, as reported previously by us. More intensive study would be necessary to elucidate the difference of biliary excretion between organic anions and cations.

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Surface Treatment of Eggshells with Low-Energy Electron Beam

  • Kataoka, Noriaki;Kawahara, Daigo;Sekiguchi, Masayuki
    • Journal of Radiation Protection and Research
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    • v.46 no.1
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    • pp.8-13
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    • 2021
  • Background: Salmonella enteritidis (SE) was the main cause of the pandemic of foodborne salmonellosis. The surface of eggs' shells can be contaminated with this bacterium; however, washing them with sodium hypochlorite solution not only reduces their flavor but also heavily impacts the environment. An alternative to this is surface sterilization using low-energy electron beam. It is known that irradiation with 1 kGy resulted in a significant 3.9 log reduction (reduction factor of 10,000) in detectable SE on the shell. FAO/IAEA/WHO indicates irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard. On the other hand, the Food and Drug Administration has deemed a dose of up to 3 kGy is allowable for eggs. However, the maximum dose permitted to be absorbed by an edible part (i.e., internal dose) is 0.1 Gy in Japan and 0.5 Gy in European Union. Materials and Methods: The electron beam (EB) depth dose distribution in the eggshell was calculated by the Monte Carlo method. The internal dose was also estimated by Monte Carlo simulation and experimentation. Results and Discussion: The EB depth dose distribution for the eggshells indicated that acceleration voltages between 80 and 200 kV were optimal for eggshell sterilization. It was also found that acceleration voltages between 80 and 150 kV were suitable for reducing the internal dose to ≤ 0.10 Gy. Conclusion: The optimum irradiative conditions for sterilizing only eggshells with an EB were between 80 and 150 kV.

A study of analytical method for Benzo[a]pyrene in edible oils (식용유지 중 벤조피렌 분석법 비교 연구)

  • Min-Jeong Kim;jun-Young Park;Min-Ju Kim;Eun-Young Jo;Mi-Young Park;Nan-Sook Han;Sook-Nam Hwang
    • Analytical Science and Technology
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    • v.36 no.6
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    • pp.291-299
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    • 2023
  • The benzo[a]pyrene in edible oils is extracted using methods such as Liquid-liquid, soxhlet and ultrasound-assisted extraction. However these extraction methods have significant drawbacks, such as long extraction time and large amount of solvent usage. To overcome these drawbacks, this study attempted to improve the current complex benzo[a]pyrene analysis method by applying the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method that can be analyzed in a simple and short time. The QuEChERS method applied in this study includes extraction of benzo[a]pyrene into n-hexane saturated acetonitrile and n-hexane. After extraction and distribution using magnesium sulfate and sodium chloride, benzo[a]pyrene is analyzed by liquid chromatography with fluorescence detector (LC/FLR). As a result of method validation of the new method, the limit of detection (LOD) and quantification (LOQ) were 0.02 ㎍/kg and 0.05 ㎍/kg, respectively. The calibration curves were constructed using five levels (0.1~10 ㎍/kg) and coefficient (R2) was above 0.99. Mean recovery ratio was ranged from 74.5 to 79.3 % with a relative standard deviation (RSD) between 0.52 to 1.58 %. The accuracy and precision were 72.6~79.4 % and 0.14~7.20 %, respectively. All results satisfied the criteria ranges requested in the Food Safety Evaluation Department guidelines (2016) and AOAC official method of analysis (2023). Therefore, the analysis method presented in this study was a relatively simple pretreatment method compared to the existing analysis method, which reduced the analysis time and solvent use to 92 % and 96 %, respectively.

Studies on the Development for Sustained Release Preparation (II):Preparation and Evaluation of Eudragit Microcapsules of Sodium Naproxen

  • Shin, Sang-Chul;Lee, Keong-Ran
    • Archives of Pharmacal Research
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    • v.16 no.1
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    • pp.50-56
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    • 1993
  • The microencapsulation of sodium naproxen with Eudragit. RS was studied by coacrtvation/phase separation process using Span 80 in mineral oil/acetone system. Various factors which affect the mciroencapsulation, e.g., stirring speed, and surfactant concentraction, Eudagit RS concentration and loading drug amounts were examined. For the evaluation of the prepared microcapsules, release rate, particle size distribution and surface appearance as well as in vivo test were carried out. The addition of n-hexane and freezing of microcapsules accelerated the hardening of microcapsules. The optimum concentration of Span 80 ti prepare the smallest microcapsules was the same value with the CMC of Span 80 in solvent system. When 1.5% (w/w) Span 80 was used, the smallest microcapsules were formed $(30.02\pm5.05\mu$ in diameter) belonging to the powder category showing smooth, round and uniform surface. The release of sodium naproxen was retarded by microencapsulation with Eudragit RS. The Eudragit RS microcapsules showed significantly increased AUC and MRT and deceased Cl/F in rabbits.

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Preparation of magnetic gelatin microspheres for the targeting of drugs

  • Lee, Kang-Choon;Koh, Ik-Bae;Oh, In-Joon
    • Archives of Pharmacal Research
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    • v.9 no.3
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    • pp.145-152
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    • 1986
  • Magnetically reponsive gelatin microspheres for the targeting of drugs have been prepared using a water-in-oil emulsion technique with chemical cross-linking of the protein. The manufacturing variables affecting microsphere size, size distribution and surface characteristics have been examined as well as the magnetic responsiveness in vitro. Sesame oil was utilized for non-aqueous phase and magentic gelatin microspheres of different size from 1. 89 to 14.88 $\mu\textrm{m}$ in mean diameter could be obtained with variation of HLB values of non-ionic surfactants. The content of magnetite which uniformly distributed throughout the microspheres was 26.7% (w/w). It was possible to control the localization of magnetic gelatin microspheres at specific sites within capilary models by using external magnetic field of under 5K gauss.

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