• YAKHAK HOEJI
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• v.41 no.6
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• pp.737-748
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• 1997

Distribution of rhEGF in the skin, plasma and several organ tissues following topical application of $^{125}I-rhEGF$ (0.4${\mu}$Ci) solution in 25% Pluronic F-127 on 154$mm^2$ normal and damaged (burned and stripped) skins of hairless mice was examined. The radioactivity in the stripped skin tissues increased as a function of time, and was 10-20 times higher than that in the normal and burned skins. The fractions of intact drug in the skin tissues were 40-60% for the normal and burned skins, and 60-80% for the stripped skin. It indicates that the stratum corneum layer behaves as a barrier for the dermal penetration of the drug. The radioactivity in the plasma was much higher for the stripped skin than for the normal and burned skins. However, the concentration of intact drug in the stripped skin was comparable to those in the normal and burned skins indicating most severe degradation (or metabolism) of the drug in the stripped skin. As a result, the fraction of intact drug in the plasma was lowest for the stripped skin (<10%). Body organ distribution of the drug was much higher for the stripped skin. The concentration in the stomach. Both in total radioactivity and intact drug, showed more than 10-times higher value than in the other organs (liver, kidney and spleen). The fraction of intact drug in each organ tissue was below 10-20%. And generally lowest for the stripped skin. The lowest fraction of the drug for the stripped skin could not be explained by the activity of the aminopeptidases in the skin since it was lower for the stripped skin than for the normal skin. Thereover, the fraction of intact drug appears to be determined by the balance between dermal uptake and systemic elimination of the drug, for example. The mechanism of dermal uptake of rhEGF was examined by topical applying 200${\mu}$l of 25% Pluronic F-127 solution containing 0.4 ${\mu}$Ci of $^{125}I-rhEGF$ and 0.14${\mu}$Ci of $^{14}C$-inulin (a marker of passive diffusion). The radioactivity of $^{125}I-rhEGF$ at each sampling time point (0.5, 1, 2, 4 and 8hr) was correlated (p<0.05) with the corresponding radioactivity of $^{14}C$-inulin. It appears to indicate the rhEGF may be uptaken into the skins mainly by the passive diffusion. This hypothesis was supported by the constant specific binding of EGF to the skin homogenates regardless of the skin models. Receptor mediated endocytosis (RME) appears to contribute negligibly, if any, to the overall uptake process.

• Mass Spectrometry Letters
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• v.12 no.3
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• pp.85-92
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• 2021

The therapeutic antibody drug market has experienced explosive growth as mAbs become the main therapeutic modality for a variety of diseases. Characterization of glycosylation that directly affects the efficacy and safety of therapeutic monoclonal antibodies (mAbs) is critical for therapeutics development, bioprocess system optimization, lot release, and comparability evaluation. The LC/MS approach has been widely used to structurally characterize mAbs, and recently attempts have been made to obtain comprehensive information on the primary structure and post-translational modifications (PTMs) of mAbs through intact protein analysis. In this study, we performed state-of-the-art LC/MS based intact protein analysis to readily identify and characterize glycoforms of various mAbs. Different glycoforms of mAbs produced in different expression cell lines including CHO, SP2/0 and HEK cells were monitored and compared. In addition, the comparability of protein molecular weight, glycoform pattern, and relative abundances of glycoforms between the commercialized trastuzumab biosimilar and the original product was determined in detail using the given platform. Intact mAb analysis allowed us to gain insight into the overall mAb structure, including the complexity and diversity of glycosylation. Furthermore, our analytical platform with high reproducibility is expected to be widely used for biopharmaceutical characterization required at all stages of drug development and manufacturing.

• Bulletin of the Korean Chemical Society
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• v.19 no.2
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• pp.194-196
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• 1998

The metabolism of dromostanolone (2α-methyl-5α- androstan-17β-ol-3-one) was studied in three adult volunteers after oral dose of 20 mg. Solvent extracts of urine obtained after enzyme hydrolysis were derivatized with MSTFA/TMCS and MSTFA/TMIS. The structures of intact drug and its metabolites were determined by gas chromatography/mass spectrometry (GC/MS) in electron impact (EI) mode. The major metabolite (2α-methyl-5α- androstan-3α-ol-17-one), its 3β-epimer, parent compound, and several hydroxylated metabolites including intact drug were detected by comparing total ion chromatograms of control urine with that of the administered sample. Two epimers of 2α-methyl-5α- androstan-3,17β-diol were detected using selected ion monitoring. The maximum excretion of dromostanolone and 2α-methyl-5α- androstan-3α-ol-17-one was reached in 6.2-15 hr. The half-life of intact dromostanolone was 5.3 hr. About 3.0% of the administered amount was found to be excreted within 95 hr as unchanged form.

• Analytical Science and Technology
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• v.15 no.3
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• pp.243-247
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• 2002

A rapid and simple determination of diazepam in intact diazepam tablets has been investigated using the near infrared spectroscopy(NIRS) combined with partial least squares regession. The separate calibration curves of 2 mg and 5 mg diazepam tablets were studied, as well as the linearity, concentration range and reproducibility of those calibration curves were evaluated. The correlation coefficients of calibration curves of 2 mg and 5 mg diazepam tablets are 0.9416 and 0.9159, respectively and the standard errors of calibration curves(SEC) are 0.018% and 0.032%, respectively.

• Analytical Science and Technology
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• v.15 no.2
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• pp.102-107
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• 2002

This paper describes a rapid determination of phenobarbital in intact phenobarbital tablets using partial least squares regression(PLSR) method of transmittance spectrum of near infrared (NIR) compared with the analytical data of liquid chromatograpy. The linearity, concentration range and precision of this analytical method are studied. The correlation coefficient of the calibration curve is 0.9983 and the standard error of calibration(SEC) is 0.14 %. Intra-day precision and Inter-day precision obtained in this method are CV = 0.45, CV =0.56, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Journal of Biomedical Engineering Research
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• v.36 no.6
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• pp.276-282
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• 2015

Recently, during the multi-level fusion with pedicle screws, interspinous spacer are sometimes substituted for the most superior level of the fusion in an attempt to reduce the number of fusion level and likelihood of degeneration process at the adjacent level. In this study, a finite element (FE) study was performed to assess biomechanical efficacies of the interspinous spacer combined with posterior lumbar fusion with a previously-validated 3-dimensional FE model of the intact lumbar spine (L1-S1). The post-operative models were made by modifying the intact model to simulate the implantation of interspinous spacer and pedicle screws at the L3-4 and L4-5. Four different configurations of the post-op model were considered: (1) a normal spinal model; (2) Type 1, one-level fusion using posterior pedicle screws at the L4-5; (3) Type 2, two-level (L3-5) fusion; (4) Type 3, Type 1 plus Coflex$^{TM}$ at the L3-4. hybrid protocol (intact: 10 Nm) with a compressive follower load of 400N were used to flex, extend, axially rotate and laterally bend the FE model. As compared to the intact model, Type 2 showed the greatest increase in Range of motion (ROM) at the adjacent level (L2-3), followed Type 3, and Type 1 depending on the loading type. At L3-4, ROM of Type 2 was reduced by 34~56% regardless of loading mode, as compared to decrease of 55% in Type 3 only in extension. In case of normal bone strength model (Type 3_Normal), PVMS at the process and the pedicle remained less than 20% of their yield strengths regardless of loading, except in extension (about 35%). However, for the osteoporotic model (Type 3_Osteoporotic), it reached up to 56% in extension indicating increased susceptibility to fracture. This study suggested that substitution of the superior level fusion with the interspinous spacer in multi-level fusion may be able to offer similar biomechanical outcome and stability while reducing likelihood of adjacent level degeneration.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.447-457
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• 1999

The purpose of this study is to prepare the adhesive type patch containing flurbiprofen, and to demonstrate the feasibility of flurbiprofen administration through the intact skin using adhesive type patch preparation. For this purpose, two pressure sensitive adhesives, Polyisobutylene(PIB) and $Gelva^{\circledR}737$, were selected from the chemical grade of polymers, and the adhesive type patches of flurbiprofen were prepared. The release rate of flurbiprofen from the PIB-based adhesive patch was higher than that from $Gelva^{\circledR}737$ based adhesive patch. The release rate of flurbiprofen from the PIB-based A-type patch with 1.0mm, 1.5mm or 2.0mm thicknesses followed the first order kinetics. In the skin permeation study, using male hairless mouse skin, a monophasic skin permeation profile was observed with 1% flurbiprofen loading dose. The inclusion of palmitic acid or SLS(0.25~0.5%) as an enhancer produced a remarkable enhancement in the skin permeation rate of flurbiprofen, and the percentile ratio of drug and enhancer appeared to be important for the effective enhancement. In the in vivo percutaneous absorption study, the plasma concentration of the optimal formulation was significantly (p<0.01) higher than that of the conventional cataplasma ($Bifen^{\circledR}$). These studies demonstrate a good feasibility of flurbiprofen administration through the intact skin using a transdermal patch, and show a possibility of the development of flurbiprofen patches.

• Journal of Environmental Health Sciences
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• v.43 no.2
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• pp.103-110
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• 2017

Objectives: This study was performed to provide basic data for the re-establishment of standards (criteria) and analytical methods for hazardous metals in nail enamel. Methods: Ten metals (lead; Pb, arsenic; As, cadminum; Cd, antimony: Sb, cobalt; Co, nikel; Ni, copper; Cu, chromium; Cr, aluminum; Al, and mercury; Hg) were measured in 67 commercial nail enamels containing glitter and/or pearls. The content of hazardous metals (excepting Hg) was determined by using an inductively coupled plasma-optical emission spectrophotometer (ICP-OES) after microwave digestion. Mercury content was measured by a mercury analyzer without any preparation. Results: The detected ranges of the intact samples were as follows: $ND-1.756{\mu}g/g$ for Pb, $ND-1.24{\mu}g/g$ for As, ND for Cd, $ND-20.41{\mu}g/g$ for Sb, $ND-12.36{\mu}g/g$ for Co, $ND-7.908{\mu}g/g$ for Ni, $0.088-79.27{\mu}g/g$ for Cu, $0.281-18.54{\mu}g/g$ for Cr, $13.78-3563{\mu}g/g$ for Al, and $ND-0.044{\mu}g/g$ for Hg. After centrifugation, the detected ranges of supernatant were as follows: $ND-0.435{\mu}g/g$ for Pb, $ND-0.504{\mu}g/g$ for As, ND for Cd, $ND-0.035{\mu}g/g$ for Sb, $ND-13.17{\mu}g/g$ for Co, $ND-0.232{\mu}g/g$ for Ni, $0.117-90.07{\mu}g/g$ for Cu, $0.174-2.787{\mu}g/g$ for Cr, and $9.459-1565{\mu}g/g$ for Al. The results of this analysis showed that the levels of heavy metals such as Pb, As, and Sb were much higher in the intact samples than those of supernatant. Conclusion: In the present study, we found that the levels of hazardous metals were significantly different depending on the status of the presence of glitter. Based on the results, we recommend that the product consumer refrain from prolonged application of nail enamel, avoid biting or chewing the nails, and wear gloves during cooking and washing dishes.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.279.1-279.1
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• 2003

NIR reflectance spectroscopy, using a fiber-optic probe was used to determine rapidly and non-destructively the content of ambroxol in intact ambroxol 30 mg (nominal content 12.5％ m/m ambroxol) tablets by collecting NIR spectra in range 1100 - 1750 nm and using PLSR calibration method. The tablets (10.3 - 15.9％ m/m ambroxol, i.e., 82 - 127％ of the nominal label content) were used 7 calibration set and 5 validation set. (omitted)