• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.73-78
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• 2010

Hydrogels are thought to be a promising delivery carrier for protein drugs because of their favorable aqueous environment compared with nano/micro-particles of hydrophobic polymer such as PLGA. In this study, nano-sized hydrogels (nanogels) were fabricated using inverse-miniemulsion polymerization method. The mean size of nanogels in range of 90-160nm and affected by the preparation parameters such as sonication time and concentration of monomer. While longer sonication time and lower concentration of acrylamide monomer showed a tendency to produce smaller nanogels and to have lower lysozyme activity, variation of bis-methylene acrylamide concentration made no difference. Although both longer soncaton time and lower acrylamide concentration increased in vitro release rate, acrylamide concentration was more effectively affected to the control of protein release rate, which indicated that the release rate of protein from nanogels affected by not only their size but also internal structure. In conclusion, nanogels prepared by inverse-miniemulsion can be a useful carrier for application of protein drug, because of simple process, minimum contact of organic solvent and high protein activity.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.239-245
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• 2016

Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.

• Toxicological Research
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• v.34 no.3
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• pp.191-197
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• 2018

In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of $90.13{\mu}g/TD$ (95% confidence interval = $87.39{\sim}92.86{\mu}g$) and a hemorrhagic titer of $10.80{\mu}g/TD$ (95% confidence interval = $10.46{\sim}11.14{\mu}g$). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

• Bulletin of the Korean Chemical Society
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• v.28 no.3
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• pp.397-402
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• 2007

Restenosis after percutaneous coronary intervention (PCI) continues to be a serious problem in clinical cardiology. To solve this problem, drug eluting stents (DES) with antiproliferative agents have been developed. Variable local drug delivery systems in the context of stenting require the development of stent manufacture, drug pharmacology and coating technology. We have worked on a system that integrates electrophoretic deposition (EPD) technology with the polymeric nanoparticles in DES for local drug delivery and a controlled release system. The surface morphology and drug loading amount of DES by EPD have been investigated under different operational conditions, such as operation time, voltage and the composition of media. We prepared poly-D,L-lactide-co-glycolic acid (PLGA) nanoparticles embedded with curcumin, which was done by a modified spontaneous emulsification method and used polyacrylic acid (PAA) as a surfactant because its carboxylic group contribute negative charge to the surface of CPNPs (?53.5 ± 5.8 mV). In the process of ‘trial and error' endeavors, we found that it is easy to control the drug loading amount deposited onto the stent while keeping uniform surface morphology. Accordingly, stent coating by EPD has a wide application to the modification of DES using various kinds of nanoparticles and drugs.

• Journal of the Korean Society of Manufacturing Technology Engineers
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• v.22 no.2
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• pp.235-240
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• 2013

This paper presents a disposable microfluidic infusion pump using the restoring force of elastomeric membrane of Polydimethylsiloxane. Microfluidic infusion pump consists of hydraulic resistance control part, elastomeric blister actuator part, drug inlet and outlet. Expanded elastomeric blister actuator continuously pushes liquid in the chamber to outlet. At same time, microchannel diameter near the outlet was controlled by thin elastomeric membrane in hydraulic resistance control part. Eventually flow rate of infused liquid is controlled by air pressure. In experimental study, the amount of the filled liquid in the blister is precisely controlled by the height of the blister. Flow rate of infused liquid could be controlled, that is, controlled release of the drug over time was possible by adjusting hydraulic resistance and restoring pressure with the blister actuator.

• YAKHAK HOEJI
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• v.56 no.4
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• pp.211-216
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• 2012

Drug dissolution test has been used for the purpose of both quality control of solid oral dosage forms and predicting in vivo drug release profiles. In this study, the dissolution profiles of buflomedil hydrochloride tablets and ticlopidine hydrochloride tablets were investigated according to the "Guidelines on Specifications of Dissolution tests for Oral dosage forms" of Korean Pharmacopoeia (KP). The analytical method using HPLC was validated. The validation was performed in terms of specificity, linearity, accuracy, precision and limit of quantitation.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.233-239
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• 2001

Local drug delivery by using biocompatible polymers has been developed in the treatment of periodontitis for many years. In the field of dental therapy, doxycycline is usually a first choice because of its broad-spectrum antibiotic activity. The strip releases antibiotics for a week, and the polymer should be degradable after a week. In this study, we prepared and evaluated the chitosan strips and nanoparticle strips containing doxycycline hydrochloride, and studied their antiacterial activity, dissoultion, and degrability in vitro. The weight of cast strip containing a 5 mg of doxycycline hydrochloride and a 45 mg of chitosan polymer was $57.67{\pm}0.17\;mg$. The release rate of doxycycline hydrochloride from the strip was measured by HPLC. The drug released from chitosan strip and nanoparticle strip was shown to be $50\;{\mu}g/mL$ in first 24 hours. In antibacterial test showed growth inhibitory activity after 24 hrs anaerobic incubation. In vitro degradability showed demolished weight of $93.74{\pm}0.08%$ chitosan strip, $82.48{\pm}1.29%$ chitosan nanoparticle strip, $2.47{\pm}1.99%$ polycarprolactione strip (control). These results showed that, with this doxycycline hydrochloride strip, it is feasible to obtain a sustained release of the drug within the periodontal pocket for seven days which may be improve for local drug delivery system for treatment of periodontal disease.

• Journal of the Korean Chemical Society
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• v.56 no.4
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• pp.473-477
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• 2012

The novel chitosan-based thermosensitive hydrogels were prepared as control-releasing drug carriers. N-carboxyethyl chitosan (ACS) was synthesized by microwave heating for 1 h through Michael addition of CS to acrylic acid in a grafting yield of 52.97%, which was proved to be a faster and more efficient way than ordinary methods. 5-Fu was modified with formaldehyde to synthesize N,N'-Bis(hydroxymethyl)-5-fluorouracil (5-Fu-OH). Then an esterification was performed using ACS and 5-Fu-OH to give 5-Fu-ACS. The new thermosensitive hydrogels were prepared by adding sodium glycerophosphate to the solution of compounds under a certain constant temperature. Simultaneously, the hydrogels' swelling rate, in vitro drug release rate and thermosensitive were studied, and found that the 5-Fu-ACS composite hydrogel had more excellent releasing effect, higher drug loading and better thermosensitive.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.109-135
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• 2006

Objective : In the present study, the author tried to investigate whether six oriental medical prescriptions named gamisingitang (SGT), gamijungtang (IJT), gamicheongpyetang (CPT), galhwengchihyosan (CHS), chwiyeontong (CYT), sigyoungcheongpyetang (SCPT) significantly affect mucin release from cultured hamster tracheal surface epithelial (HTSE) cells. Methode : Confluent HTSE cells were inetabolically radiolabeled with $^{3}H-glucosamine$ for 24 hrs and chased for 30 min in the presence of drugs aforementioned, respectively, to assess the effect of each drug on $^{3}H-mucin$ release. Possible cytotoxicities of effective drugs were assessed by measuring lactate dehydrogenase(LDH) release. Additionally, total elution profiles of control spent media and treatment sample (CPT, CHS, SCPT and CYT) through Sepharose CL-4B column were analysed and effect of CPT, CHS and CYT on MUC5AC mRNA expression in cultured HTSE cells were invsetigated. Results : (1) SGT and IJT did not affect mucin release without cytotoxicity; (2) CPT, SCPT and CHS significantly stimulated mucin release from cultured HTSE cells, with significant cytotoxicity; (4) CPT, CHS, SCPT and CYT chiefly affected the 'mucin' release and did not affect significantly the release of the releasable glycoproteins with less molecular weight than mucin. This result suggests that the four herbal prescriptions specifically affect the release of mucin ; (5) CTP and CHS did not significantly affect the expression levels of MUC 5AC mRNA, however, CYT significantly inhibit the expression levels of MUC 5AC mRNA. Conclusion : CYT can decrease the synthesis of mucin at gene level in cultured HTSE cells.

• Toxicological Research
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• v.33 no.3
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• pp.225-231
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• 2017

National reference standards (NRSs) for biologics are established through potency estimation by a multi-center joint study of standard materials used in the approval process for national lot release and quality control of vaccines, blood products, and other biologics. In this study, a stability evaluation was conducted to determine whether the potency of NRSs for six blood products was being maintained at a consistent level in Korea. The present study conducted real-time stability tests via in-vivo/in-vitro bioassay on NRSs for blood coagulation factor VIII concentrate (2nd standard), antithrombin concentrate, prekallikrein activator, anti-hepatitis B immunoglobulin, blood coagulation factor IX concentrate, and anti-tetanus human immunoglobulin, as well as a trend analysis using cumulative annual results. The real-time stability test results showed that the mean potency of six NRSs was all within the control limit. In the trend analysis, the potency of NRS for blood coagulation factor VIII concentrate (2nd standard) showed a decreasing trend, while the potency of all other products had been stably maintained. The present study confirmed that the mean potency of NRSs for six blood products had been stably maintained in Korea. The findings of the present study establish a foundation that can ensure the quality of NRSs for biologics in Korea, and it is expected to make a major contribution to the supply of high-quality biologics.