• Title/Summary/Keyword: 단백질 약물

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Release Properties of BSA from Pectin Heads for Colonic Drug Delivery (Colonic Delivery를 위한 펙틴 비드로부터 BSA의 방출 특성)

  • 최춘순;박상무;송원현;이창문;이기영;김동운;김진철
    • KSBB Journal
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    • v.18 no.2
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    • pp.161-164
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    • 2003
  • Oral drug delivery system using pectin gel was developed for colon-targeting of peptide drug. BSA(bovine serum albumin)-loaded pectin and pectin-alginate beads were prepared for drug release properties in vitro. Morphological studies by electron microscopy indicated that pectin and pectin-alginate beads were spherical in shape and approximately 1.0 mm. In order to find the suitable beads, effects of cross-linking agents (calcium chloride or zinc acetate) and drying temperature of beads were investigated. Drug release decreased with concentration of cross-linking agents and drying temperature. For colonic drug delivery from pectin and pectin-alginate beads, pectin degradable enzymes were added at 5 hrs from the beginning of drug release. After addition of enzymes, drug release was suddenly increased against free enzymes. Therefore, pectin and pectin-alginate beads can be promised as useful drug release carriers for colon-targeted delivery.

The Production of Protein-loaded Poly(lactide-co-glycolide) Microparticles using Supercritical Carbon Dioxide (초임계 PGSS 법을 이용한 Poly(lactide-co-glycolide)와 단백질의 마이크로복합체 제조에 관한 연구)

  • Song, Eun-Seok;Jung, Heon-Seop;Lee, Hanho;Kim, Jae-Duck;Kim, Hwayong;Lee, Youn-Woo
    • Clean Technology
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    • v.12 no.2
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    • pp.53-61
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    • 2006
  • A PGSS (Particles from Gas Saturated Solutions) process designed to generate nano-particles using supercritical fluids has been conducted for the fabrication of Poly(lactide-co-glycolide) (PLGA) microparticles that encapsulate a protein drug. It is demonstrated that the polymer and the dry powder of a protein can be mixed under supercritical carbon dioxide conditions and that the protein component retains its biological activity. In this experiment, the mixture of polymer which is plasticized and dry powder protein was sprayed to form solid polymer that encapsulate the protein. It is found that supercritical fluid process give fine tuning of particle size and particle size distribution by simple manipulations of the process parameters. Porous particles were formed with irregular shape. Protein encapsulated in the polymer was found to have enzymatic activity without significant loss of its initial value.

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담자균류의 약효 성분의 개발에 관한 연구

  • 김병각;권지연;복진우;최웅칠
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.141-141
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    • 1993
  • 말징버섯 Calvatia craniformis의 culture broth 40 liter를 여과하여 얻은 균사채를 열수 추출하여 진한 갈색 건조분말(Fr. A) 13.1g을 분리하였다. Fr. A에 대하여 DEAE-cellulose ion chromatography를 시행하여 중성분획인 흰색 분말 (Fr. B) 2.50g을, 산성분획인 갈색 분말 (Fr. C) 3.50g을 각각 분리하였다. Fr. B 500mg에 대하여 Sepharose CL-4B gel filtration chromatography를 시행하여 흰색분말 Fr. D(Calvatan) 350mg을 분리하였다. Calvatan 350mg에 대하여 Con A-Sepharose 4B affinity chromatography를 적용하여 미흡착 분획인 Fr. F($\alpha$-form)와 흡착 분획인 Fr. E ($\beta$-form)로 정제하였다. 항암작용의 기전을 구명하고자 마우스에 대하여 면역학적 실험을 시행하였다. macrophage의 활성에 대한 영향을 조사하였던 바, 투여군의 활성화된 macrophage에 의해 유리되는 superoxide anion의 양은 대조군에 비해 1.4배 증가하였고 Calvatan 투여군의 용혈반 형성세포(PFC)는 대조군에 비해 3.1배 증가하였다. 화학 분석에 의해, Calvatan은 다당체 87.2%, 단백질 1.8% 및 hexosamine 1.3%로 구성되어 있었다. 따라서 항암성 분획들은 protein-bound polysaccharide임을 알 수 있었다. 또한 각 분획의 다당체를 구성하고 있는 단당류는 glucose, galactose, mannose 및 xylose 였으며 단백질 부분은 16종의 아미노산으로 구성되어 있었다. IR 스펙트럼은 3300-3400 $cm^{-1}$에서 0-H stretching frequency, 2900 $cm^{-1}$ 에서 C-H stretching frequency, 1630 $cm^{-1}$ 에서 C-0 stretching frequency. 1000-1100 $cm^{-1}$에서 C-H 및 C-0 bending frequency를 나타내는 다당체의 전형적인 특성을 보여주었다.을 보여주었다.

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Effects of Silkworm Powder on Blood Glucose and Lipid Levels in NIDDM(Type II) Patients (인슐린 비의존형(Type II) 당뇨환자에서 누에분말 섭취가 혈당 및 혈중지질농도에 미치는 영향)

  • 조미란;조여원;정성현;류재환
    • Journal of Nutrition and Health
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    • v.31 no.7
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    • pp.1139-1150
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    • 1998
  • The purpose of this study is to investigate the effects of the silkworm powder on blood levels of glucose, Hb Alc, insulin, and lipids. Thirty-one NIDDM patients from Kyung Hee Medical Center were divided into two groups : patients with silkworm powder supplements and drug treatments(Drug diabetes) and patients with silkworm powder supplement only(Non-drug diabetes). For the control group, age-matched subjects were recruited. During the 4 weeks of the experimental period, silkworm powder(500mg/mea1) was given to the subjects right after each meal. Nutritional assessments and dietary education were carried out periodically, and body weight and blood pressure were measured when patients visited the hospital. Overnight fasting and 2-h postprandial blood glucose levels were measured at 2 week intervals. The blood levels of insulin, Hb Alc, and lipids were measured before and after the supplements. The mean ages of the three groups were 56.7-59.6 years old. The height, weight, and BMI did not differ among the groups. The fasting blood glucose levels were 138.1$\pm$22.0mg/dl for the Drug treated diabetes group, 175.0$\pm$32.0mg/dl for the Non-drug diabetes group, and 108. 3$\pm$16.gmg/dl for the control group at the begining of the supplement. After 4-wks of supplements, the blood levels of glucose tended to decrease in all three experimental groups. Before the supplements, the 2-h postprandial blood glucose levels of the Drug diabetes, Non drug diabetes, and control groups were 244.7$\pm$62.6mg/dl, 272.4$\pm$40.1mg/dl, and 147.7$\pm$28.0mg/dl, respectively. After the supplement, the levels were 197.2$\pm$30.gmg/dl, 208.6$\pm$ 56.6mg/dl, and 151.3$\pm$30.3mg/dl, respectively. This shows that silkworm powder tended to lower blood levels by 19.4% and 23.4% in NIDDM patient groups. However, the changes in the blood levels of insulin, Hb Alc, ind lipids were not observed after the supplement. In conclusion, the present study has demonstrated that silkworm powder has a tendency to decrease 2-h postprandial blood glucose levels, but it should be used with caution in controlling the diabetes. (Korean J Nutrition 31(7) 1139-1150, 1998)

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Preparation of Protein-coated Cationic Liposomes Containing Doxorubicin and Their Binding Property of Blood Plasma Protein (독소루비신을 함유하고 단백질로 수식된 양이온성 리포솜의 제조 및 혈장 단백흡착 특성)

  • Kim, Sung-Kyu;Jung, Soon-Hwa;Jung, Suk-Hyun;Seong, Ha-Soo;Chi, Sang-Cheol;Cho, Sun-Hang;Shin, Byung-Cheol
    • Journal of the Korean Chemical Society
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    • v.52 no.1
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    • pp.57-65
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    • 2008
  • are nanometer or micrometer scale vesicles that can be used as drug delivery carriers. However, plain liposomes are plagued by rapid opsonization, making their circulation time in bloodstream be shortened. In this study, model protein, bovine serum albumin (BSA)-coated liposomes were prepared by coating cationic liposomes with BSA molecules at higher pH than isoelectric point of BSA. The BSA molecules coated on the liposomal surface were denatured by thermal treatment at above 60oC. While both plain and cationic liposomes had about mean particle diameter of 1041 nm, BSA-coated cationic liposomes (BCL) had mean particle diameter of 1091 nm. Encapsulation of model drug, doxorubicin (DOX), in liposomes were carried out by using remote loading method and the loading efficiency of DOX to liposomes was about 90%. The mean particle diameter of BCL did not increase in blood plasma and adsorption of plasma protein was much less than plain or cationic liposomes. These results suggest that BCL can be used as a long-circulating liposomes in bloodstream.

Electrospraying of Micro/Nano Particles for Protein Drug Delivery (단백질 약물 전달을 위한 마이크로/나노 입자의 전기분무 제조법)

  • Yoo, Ji-Youn;Kim, Min-Young;Lee, Jong-Hwi
    • Polymer(Korea)
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    • v.31 no.3
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    • pp.215-220
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    • 2007
  • The control of the surface energy by electrohydrodynamic force provides electrospraying with various potential advantages such as simple particle size control, mono-dispersity, high recovery, and mild processing conditions. The advantages are quite helpful to improve the stability of protein drug and control its release. Herein, the nano-encapsulation of protein drugs using electrospraying was investigated. Albumin as a model protein was processed using uniaxial and co-axial electrospraying, and chitosan, polycaporlactone (PCL), and poly (ethylene glycol) (PEG) were used as encapsulation materials. The major processing parameters such as the conductivity of spraying liquids, flow rate, the distance of electrical potential gradient, etc were measured to obtain the maximum efficiency. In the chitosan systems, mean particles size decreases as flow rate and the distance between nozzle and the collecting part decreases. In the uniaxial technique of the PCL systems, mean particles size decreases as flow rate decreases. In the coaxial technique of the PCL systems, it was found that the particles size gets larger under the application of the higher ratio of inner-to-outer liquid flow rates. The primary particles formed out of an electrospraying nozzle showed narrow particle size distribution, but once they arrived to the collecting part, aggregation behavior was observed obviously. Efficient nano-encapsulation of albumin with PCL, PEG, and chitosan was conveniently achieved using electrospraying at above 12 kV.

Proteomic analysis of human serum from patients with temporal lobe epilepsy (측두엽 간질환자의 혈청에서 프로테오믹스기법을 활용한 질병관련 단백질 동정)

  • Lee, Chang Woo;Yu, Seung Taek;Choi, Ha Young;Koh, Bun Jeong;Kwak, Yong Guen
    • Clinical and Experimental Pediatrics
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    • v.52 no.5
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    • pp.567-575
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    • 2009
  • Purpose : Epilepsy affects more than 0.5% of the world's population. It has a large genetic component and is caused by electrical hyperexcitability in the central nervous system. Despite its prevalence, the disease lacks definitive diagnostic serological biomarkers. To identify potential biomarkers for epilepsy by a convenient method, we analyzed the expression of serum proteins, reflecting alterations in the patient's proteomes. Methods : We compared two-dimensional electrophoretic band patterns of human sera from eight patients with temporal lobe epilepsy (TLE) with those of eight control subjects. The differentially expressed bands were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization quadrupole time-of-flight mass spectrometry. esults : Twelve proteins were differentially expressed in the TLE group, of which 6 were identified. Expression of haptoglobin Hp2, PRO2675, immunoglobulin heavy chain constant region gamma 2, an unnamed protein, and three unidentified proteins were upregulated in serum from the patients with TLE, whereas those of major histocompatibility complex (MHC) class I antigen, plasma retinol-binding protein precursor, and three unidentified proteins were downregulated in these patients. After resection of the epileptogenic zone, the expressions of MHC class I antigen, immunoglobulin heavy chain constant region gamma 2, two of the downregulated unidentified proteins, and one of the upregulated unidentified proteins returned to the normal range. Conclusion : The 12 serum proteins in this study are potentially useful biomarkers for the diagnosis and monitoring of TLE.

Effect of ethanol concentration on the infrared spectroscopic characteristics of silk beads (알코올의 농도에 따른 실크 비드의 적외선 분광 특성)

  • Kim, Sung-Kuk;Jo, You-Young;Lee, Kwang-Gill;Kim, Kee-Young;Kim, Hyun-bok;Kweon, HaeYong
    • Journal of Sericultural and Entomological Science
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    • v.53 no.2
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    • pp.118-123
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    • 2015
  • The structural transition of silk protein has been induced by various method including alcohol treatment. To know the effect of alcohol concentration on silk beads conformation, silk beads were prepared in different alcohol concentration (100%, 70%, and 50%) and then examined the infrared spectra of silk beads. Silk beads prepared in 100% alcohol showed at $1265cm^{-1}$ attributed ${\beta}-sheet$ conformation and did not showed a characteristic absorption peak from model drug. However, silk beads in 70% and 50% alcohol showed some peaks originated from model drug including $2933cm^{-1}$, $1069cm^{-1}$, and $973cm^{-1}$. These results means that the micro-environment of silk beads was affected by alcohol concentration.

Association of Genetic Variations with Pemetrexed-Induced Cytotoxicity in Non-Small Cell Lung Cancer Cells (비소세포폐암 세포주에서 pemetrexed의 세포독성과 유전학적 다형성과의 상관성 조사)

  • Yoon, Seong-Ae;Choi, Jung-Ran;Kim, Jeong-Oh;Shin, Jung-Young;Zhang, XiangHua;Kang, Jin-Hyoung
    • Journal of Life Science
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    • v.20 no.1
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    • pp.103-112
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    • 2010
  • Pemetrexed has demonstrated clinical activity in non-small cell lung cancer (NSCLC) as well as other solid tumors. It transports into the cells via reduced folate carrier (RFC) and is polyglutamated by folypolyglutamate synthetase (FPGS). Pemetrexed directly inhibits several folate-dependent enzymes such as thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). We investigated the effects of genetic variations and the expression of RFC, FPGS, TS and DHFR enzymes on drug sensitivity to pemetrexed in NSCLC cells. Polymorphisms in RFC, FPGS, and DHFR were genotyped in four NSCLC cells - A549, PC14, HCC-1588, and H226. Real-time RT-PCR and Western blot was performed to evaluate mRNA transcripts and protein of these genes. The cytotoxicity of pemetrexed was measured by SRB assay. In PC14 and H226 cells, increased mRNA expressions of RFC and FPGS were associated with higher cytotoxicity to pemetrexed. 2R/2R genotype of TS and its increased mRNA expression were associated with drug resistance to pemetrexed in A549 cells, whereas 3R/3R genotype in TS with decreased mRNA expression was associated with higher sensitivity in H226 cells. After pemetrexed treatment, an inverse change of DHFR mRNA and protein expression was found. The strongest linkage disequilibrium (LD) was discovered between-1726C>T and -1188A>C SNP of DHFR gene. Our findings suggest the cytotoxic effect of pemetrexed may be associated with genetic polymorphisms and the expression level of genes involved in pemetrexed metabolisms in NSCLC cells.

Cobra (Ophiphagus hannah) 독으로부터 세포 독성 단백질의 분리

  • 김영식;이병무;안미영;박재갑;현진원;임경화;박호군
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.205-205
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    • 1994
  • 동물, 곤충, 해조류 등으로 부터 얻어진 독소는 해로운 것으로 알려져 있지만 의학적으로 유용한 화합물을 내포하고 있다. 본 연구는 이러한 점에 착안하여 독사, 또는 곤충의 독 30여종을 대상으로 위암 세포인 SNU-1에 대해서 MTT assay에 의한 세포 독성 시험을 실시하였다. 이 중 세포 독성 활성이 가장 놓은 코브라 계통인 Ophiphagus hannah의 독으로 부터 세포 독성 물질의 정제를 시도하였다. HPLC-GPC와 HPLC-lEX 또는 RP-HPLC를 이용하여 정제하였고 각 분획들을 암세포주에 대해서 시험하였다. TSK-2000SW로 부터 2개의 분획을 얻어 분획 I에서 $IC_{50}$/ 의 값이 0.5 - 3 $\mu\textrm{g}$/ml의 범위 내에서 확인되었다. 분자량이 작은 분획 II에서는 세포독성이 작게 나타났지만 농축하여 성분 분석을 시도하였다. 분획 I을 RP-HPLC를 이용하여 TFA와 acetonitrile의 linear gradient에 의해 더욱 분리를 하였고, phopholipase $A_2$ 활성의 가능성도 측정하였다. 분획 II는 Mono S 칼람을 이용하여 ammonium acetate농도에 따른 pH gradient에 의한 분리를 시도하여 순도를 SDS-PAGE에 의해서 확인하였다. 각각의 크로마토그리피로 부터 얻은 분획에 대해서 세포 독성을 실시중에 있으며 성질도 동정중에 있다.

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