• Title/Summary/Keyword: Biological half life

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Preparation and Evaluation of Semi-Solid Nifedipine Implants of Poly(ortho esters) (폴리오르소에스터를 이용한 니페디핀의 반고형 이식제제의 제조 및 평가)

  • Lee, Sae-Byul;Park, Joo-Ae;Lee, Seung-Jin;Kim, Kil-Soo
    • Journal of Pharmaceutical Investigation
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    • v.29 no.2
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    • pp.93-98
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    • 1999
  • Semi-solid poly(ortho esters) (POE) were prepared to provide bioerodible carriers for sustained drug delivery systems of nifedipine in the treatment of cardiovascular disease. As the POE has viscous behavior at room temperature, a significant advantage of this polymer is that it can be injected without any surgical intervention. The POE was synthesized by a transesterification reaction between 1,2,6-hexanetriol and trimethyl orthoacetate and the nifedipine release from POE was studied in vitro. The release rate of nifedipine decreased with increasing the amount of nifedipine and the diethanolamine dispersed in the polymer. But the excess amounts, above 3%, of diethanolamine retarded the release of nifedipine. In vivo biocompatibility studies were carried out in rats with nifedipine loaded POE. Histopathological analysis showed that nifedipine loaded POE implants were well-tolerated by rats when used subcutaneously. In case of the rats implanted POE containing diethanolamine, tissue necrosis and inflammation were occured. Pharmacokinetic studies of nifedipine loaded POE implants were carried out in rabbits. In all cases, plasma concentrations of nifedipine were maintained over 15 ng/ml for at least 360 hours and biological half $life(t_{1/2})$ and mean residence time(MRT) were increased by addition of diethanolamine.

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Studies on Bioavailability of Commercially Available Sulfamethoxazole and Trimethoprim Tablets in Rabbits (시판 설파메톡사졸-트리메토프림정의 생체내 이용율에 관한 연구)

  • Choi, Jun-Shik;Kim, Kyoung-Ok;Burm, Jin-Pil
    • Journal of Pharmaceutical Investigation
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    • v.17 no.3
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    • pp.135-139
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    • 1987
  • This study was attempted to investigate the dissolution rate and the bioavailability of commercially available sulfamethoxazole and trimethoprim (SMX-TM) tablets in rabbits. The dissolution test was conducted in artificial gastric juice by basket method with eight SMX-TM tablets which were chemically equivalent. According to the dissolution rate, SMX-TM tablets were divided into four groups, such as rapid, intermediate, slow and very slow groups for the bioavailability test in rabbits. The results were as follows: 1) The dissolution rate of brand A was most rapid but brand H was most slow in artificial gastric juice. 2) Area under the blood concentration curve was larger in the order of brand A > C > E > H in rabbits. 3) There was a little difference in pharmacokinetic parameters such as biological half life, absorption rate constant and $t_{max}$. 4) The relationship between the dissolution rate and relative bioavailability was significant in brand A, C, E and H. From the results of this experiment, the bioavailability of SMX-TM tablets in rabbits may be predicted from the results of dissolution rate studies.

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Residual Pattern of Procymidone and Chlorothalonil in Grape During the Period of Cultivation and Storage (포도의 재배 및 저장기간 중의 Procymidone 및 Chlorothalonil의 잔류량변화)

  • Ko, Kwang-Yong;Kim, Kum-Hee;Lee, Kyu-Seung
    • Korean Journal of Environmental Agriculture
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    • v.23 no.1
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    • pp.47-51
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    • 2004
  • In order to know the residual pattern of pesticides and predict to the degradation period until below MRL we experimented procymidone and chlorothalonil for grape which were the most detected pesticide in grape by NAQS(National Agricultural product Quality management Service) survey. In this experiment we sprayed those pesticides 10 days before harvest and analyzed 0, 1, 2, 3, 5, 7, 10 day sample to establish logical equation and to calculate $DT_{50}$. Also the same day samples stored at $4^{\circ}C$ and $20^{\circ}C$, which were compared their degradation patterns. During the cultivating period, the residue amount of procymidone was changed from 1.85 mg/kg (0 day) to 0.33 mg/kg (10 day), $DT_{50}$ was 3.5 days, and chlorothalonil was changed from 5.5 mg/kg (0 day) to 3.49 mg/kg (10 day), $DT_{50}$ was 4.4 days. During the storage period, $DT_{50}$ of procymidone and chlorothalonil at $4^{\circ}C$ were 10.5 and 7.6 days, and 6.3 and 6.1 days at $20^{\circ}C$, respectively.

Multi-Channel Vision System for On-Line Quantification of Appearance Quality Factors of Apple

  • Lee, Soo Hee;Noh, Sang Ha
    • Agricultural and Biosystems Engineering
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    • v.1 no.2
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    • pp.106-110
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    • 2000
  • An integrated on-line inspection system was constructed with seven cameras, half mirrors to split images. 720 nm and 970 nm band pass filters, illumination chamber having several tungsten-halogen lamps, one main computer, one color frame grabber, two 4-channel multiplexors, and flat plate conveyer, etc. A total of seven images, that is, one color image form the top of an apple and two B/W images from each side (top, right and left) could be captured and displayed on a computer monitor through the multiplexor. One of the two B/W images captured from each side is 720nm filtered image and the other is 970 nm. With this system an on-line grading software was developed to evaluate appearance quality. On-line test results with Fuji apples that were manually fed on the conveyer showed that grading accuracies of the color, defect and shape were 95.3%, 86% and 88.6%, respectively. Grading time was 0.35 second per apple on an average. Therefore, this on-line grading system could be used for inspection of the final products produced from an apple sorting system.

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Long-acting Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) with a Trimer-Structured Polyethylene Glycol

  • Jo, Yeong-Woo;Lee, Mee-Yong;Choi, Yun-Kyu;Lee, Sung-Hee;Kang, Soo-Hyoung;Na, Kun;Youn, Yu-Seok;Choi, Eung-Chil
    • Journal of Pharmaceutical Investigation
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    • v.40 no.6
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    • pp.379-386
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    • 2010
  • Mono PEGylated rhG-CSF (PEG-G-CSF) prepared by utilizing unique PEG was purified and characterized by cation-exchange chromatography. A unique, trimer-structured PEG was chosen for PEGylation of rhG-CSF among various PEG moieties. The in-vitro bioactivity, stability, and pharmacokinetics of mono-PEG-G-CSF were examined and compared to those of native rhG-CSF. Mono PEG-G-CSF exhibited reduced in-vitro bioactivity to native rhG-CSF but showed an excellent in-vivo bioactivity and stability. Furthermore, it showed markedly reduced clearance in rats, thereby increasing the biological half-life by about 4.5-fold compared to that of native rhG-CSF. The results suggest that this unique, trimer-structured 23 kDa PEG can provide advantages to improve the bioactivity of therapeutic proteins in clinical use.

In vitro and in vivo application of anti-cotinine antibody and cotinine-conjugated compounds

  • Kim, Hyori;Yoon, Soomin;Chung, Junho
    • BMB Reports
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    • v.47 no.3
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    • pp.130-134
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    • 2014
  • The combination of a high-affinity antibody to a hapten, and hapten-conjugated compounds, can provide an alternative to the direct chemical cross-linking of the antibody and compounds. An optimal hapten for in vitro use is one that is absent in biological systems. For in vivo applications, additional characteristics such as pharmacological safety and physiological inertness would be beneficial. Additionally, methods for cross-linking the hapten to various chemical compounds should be available. Cotinine, a major metabolite of nicotine, is considered advantageous in these aspects. A high-affinity anti-cotinine recombinant antibody has recently become available, and can be converted into various formats, including a bispecific antibody. The bispecific anti-cotinine antibody was successfully applied to immunoblot, enzyme immunoassay, immunoaffinity purification, and pre-targeted in vivo radioimmunoimaging. The anti-cotinine IgG molecule could be complexed with aptamers to form a novel affinity unit, and extended the in vivo half-life of aptamers, opening up the possibility of applying the same strategy to therapeutic peptides and chemical compounds.

LC-MS/MS Assay Validation for a New Immune Modulator, JHL45, and its Major Metabolite in Plasma: Application to Pharmacokinetic Studies in Rats

  • Baek, In-Hwan;Chae, Jung-Woo;Song, Gyu-Yong;Kwon, Kwang-Il
    • Bulletin of the Korean Chemical Society
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    • v.30 no.11
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    • pp.2631-2636
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    • 2009
  • JHL45, a novel immune modulator for anti-atopic dermatitis and allergic airway disease, was synthesized from decursin isolated from Angelica gigas. In order to conduct a pharmacokinetic study of JHL45, an analytical method, ideally one that uses a minimal amount of biological sample must first be validated. In this study, a HPLC-MS/MS method was developed and validated for the quantification of JHL45 and its major metabolite, (+)-decursinol, from 10 ${\mu}L$ of rat plasma. JHL45 was stable under the analysis conditions, and intra- and inter-day accuracies exceeded 90.06%, with a precision variability ${\leq}$ 13.16% for each analyte. The mean values for Cmax, AUC8h, half-life of JHL45 in rats after intravenous administration of 5 mg/kg JHL45 were 24.59 μg/mL, 10.02 ${\mu}g{\cdot}h/mL$, and 1.88 h, respectively. The validated method herein will be useful for further pharmacokinetic studies of JHL45, as well as in preclinical and clinical phases.

The role and characterization of .betha.-1, 3-glucanase in biocontrol of fusarium solani by pseudomonas stutzeri YPL-1

  • Lim, Ho-Seong;KiM, Sang-Dal
    • Journal of Microbiology
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    • v.33 no.4
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    • pp.295-301
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    • 1995
  • An antifungal Pseudomonas stutzeri YPL-1 produced extracellular chitinase and .betha.-1, 3-glucanase that were key enzymes in the decomposition of fungal hyphal walls. These lytic extracellular enzymes markedly inhibited mycelial growth of the phytopathogenic fungus Fusarium solani. A chitinase from P. stutzeri YPL-1 inhibited fungal mycelial growth by 87%, whereas a .betha.-1, 3-glucanase from the bacterium inhibited growth by 53%. Furthermore, co-operative action of the enzymes synergistically inhibited 95% of the fungal growth. The lytic enzymes caused absnormal swelling and retreating on the fungal hyphal walls in a dual cultures. Scanning electron microscopy clearly showed hyphal degradation of F. solani in the regions interacting with P. stutzeri YPL-1. In an in vivo pot test, P. stutzeri YPL-1 proved to have biocontrol ability as a powerful agent in controlling plant disease. Planting of kidney bean (Phaseolus vulgaris L.) seedlings with the bacterial suspension in F. solani-infested soil significantly suppressed the development of fusarial root-rot. The characteristics of a crude preparation of .betha.-1, 3-glucanase produced from P. stutzeri YPL-1 were investigated. The bacterium detected after 2 hr of incubation. The enzyme had optimum temperature and pH of 40.deg.C and pH 5.5, respectively. The enzyme was stable in the pH range of 4.5 to 7.0 and at temperatures below 40.deg.C, with a half-life of 40 min at 60.deg.C.

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Bioavailability of Commercially Available Aspirin Tablets in Human (시판 아스피린 정제의 생체내 이용율)

  • Lee, Jin-Hwan;Choi, Jun-Shik;Baik, Chai-Sun;Burm, Jin-Pil
    • Journal of Pharmaceutical Investigation
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    • v.19 no.3
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    • pp.131-136
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    • 1989
  • This study was attempted to investigate the dissolution rate and the bioavailability after oral administration of commercially available aspirin tablets in normal volunteers. The dissolution test was conducted in artificial gastric juice using basket method with three aspirin preparations (A, B and C) which were chemically equivalent. The results were as follows; The dissolution rate was higher in the order of three different brand B>A >C. Area under the blood concentration and peak blood concentration were larger in the order of brand A>B>C. Absorption rate constant and peak time were larger in the order of brand B>A>C, and there was a little difference in elimination rate constant and biological half-life. The correlation of the dissolution rate and absorption rate constant, as well as correlation of the dissolution rate and peak time showed significant linear relationship respectively. From the results of this experiment, it can be concluded that the bioavailability of aspirin tablets showed much difference according to commercial preparations, and that the bioavailability of aspirin tablets in human may be predicted from the results of dissolution rate studies.

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Recombinant human BMP-2/-7 heterodimer protein expression for bone tissue engineering using recombinant baculovirus expression system

  • Park, Seung-Won;Goo, Tae-Won;Kim, Seong Ryul;Choi, Kwang-Ho
    • International Journal of Industrial Entomology and Biomaterials
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    • v.32 no.2
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    • pp.49-53
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    • 2016
  • Bone morphogenetic proteins (BMPs) are essential growth factors for bone formation, skeletal development and bone regeneration. The BMP-2/7 heterodimer is known to have remarkable effects on osteogenic induction that are even stronger than the BMP-2 or BMP-7 homodimers. We designed a recombinant human BMP-2/7 (rhBMP-2/7) heterodimer protein with four glycine residues between BMP-2 and BMP-7 protein to facilitate free bond rotation of domains. The Baculovirus Expression Vector System (BEVS) is routinely used to produce recombinant proteins in the milligram scale. In this study, the BEVS was used to express the rhBMP-2/7 protein whrer the recombinant baculovirus was recovered in the host Sf9 cells. To confirm the biological activity of rhBMP-2/7 protein secreted from the BEVS as an osteogenic differentiation and induction factor, we measured the BMP-induced ALP activity. rhBMP-2/7 could be used as an alternative to BMPs to overcome limitations like short half-life and requirement for high concentrations. Furthermore, rhBMP-2/7 may be an efficient tool for various application studies such as bone regeneration and skeletal development.