• Bulletin of the Korean Chemical Society
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• v.30 no.6
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• pp.1341-1348
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• 2009

Electrocatalytic oxidation of two anti-inflammatory drugs (Mefenamic acid and Indomethacin) was investigated on a cobalt hydroxide modified glassy carbon (CHM-GC) electrode in alkaline solution. The process of oxidation and its kinetics were established by using cyclic voltammetry and chronoamperometry techniques as well as steady state polarization measurements. Voltammetric studies indicated that in the presence of under study drugs, the anodic peak current of low-valence cobalt species increased, followed by a decrease in the corresponding cathodic current. This result indicates that the drugs were oxidized via cobalt hydroxide species immobilized on the electrode surface via an E$\acute{C}$ mechanism. A mechanism based on the electrochemical generation of Co (IV) active sites and their subsequent consumption by the drugs in question was also investigated. The constants rate of the catalytic oxidation of the drugs and the electron-transfer coefficients reported.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.3
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• pp.191-195
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• 2004

Drug delivery systems that are based on pectin have been studied for colon specific delivery using the specific activity of colon microflora. The aim of this study was to design a novel method of manufacturing pectin microspheres without oils and surfactants and to investigate the potential use of the pectin microspheres as an oral colon-specific drug carrier. The pectin microspheres were successfully formed using the spray drying method and crosslinking with calcium chloride. From the crosslinked pectin microspheres, indomethacin (IND) release was more suppressed than its release from non-crosslinked microspheres. In a low pH (pH 1.4) environment, the pectin microspheres released IND at an amount of about 18${\pm}$2% of the total loaded weight for 24 h while the release rate of IND was stimulated at neutral pH (pH 7.4). IND release from the pectin microspheres was increased by the addition of pectinase. The results clearly demonstrate that the pectin microspheres that were prepared by the spray drying and crosslinking methods are potential carriers for colon-specific drug deliveries.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1538-1542
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• 2006

The study was designed to investigate the effects of MokhwyangJoki-san Extract (MJSE) on the change of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and further to determine the mechanism of MJSE. The results in normal rats were as follows ; MJSE significantly increased rCBF in a dose-dependent manner, and MABP did not change in a dose-dependent manner. This results were suggested that MJSE significantly increased rCBF by dilating pial arterial diameter. The MJSE-induced increase in rCBF was significantly inhibited by pretreatment with methylene blue (10 ${\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase, and was not changed by indomethacin (1 ${\mu}g/kg$, i.p.), an inhibitro of cyclooxygenase. The MJSE-was not changed MABP was decreased by pretreatment with indomethacin but was not changed by methylene blue. This results were suggested that the mechanism of MJSE was mediated by guanylate cyclase.

• Journal of Pharmaceutical Investigation
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• v.6 no.3
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• pp.58-69
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• 1976

It is well established that dissolution is freruently the rate limiting step in the gastrointestinal absorpton of a drug from a solid dosage from. The relationship between the dissolution rate and absorption is particularly distinct when considering drugs of low solubility. Consequently, numerous attempts have been made to modify the dissolution characteristics of poorly water soluble drugs. Since dissolution rate is directly proportional to surface area, one may increase the rate by decreasing the particle size of the drug. Levy has considered a number of methods by which a drug may be presented to the GI fludids in finely divided from. The direct method is the utilization of microcrystalline or micronized particles. A second method involves the administration of solutions from which, upon dilution with gastric fluids, the dissolved drug will precipitate in the form of very fine particles. A more unique way of obtaining microcrystalline dispersions of a drug has been ercently suggested by Sekiguchi et al. They have first proposed the formation of a eutectic mixture of a poorly water soruble drug with a physiologically inert, easily soluble carrier. When such systems are exposed to water or GI fluids, the soluble carrier will dissolve rapidly and the finely dispersed drug particles will then be released. It has been suggested by Shefter and Higuchi that the formation of crystalline solvate could be a powerful tool in affecting rapid disslution of highly insoluble substances. Goldberg et al. have noted that the formation of solid solution could reduce the particle size to a minimum and increase the dissolution rate as well as the solubility of the durgs. It has also been shown that the rates of solution of drugs were appreciably increased by coprectipitating the drug with soluble polymers. The increase was found to be sensitive to the method of preparation, the molecular weight of polymer and the particular ratio of drugs to polymer. Although several investigations have demontrated that the solubility and/or dissolution rates of drugs can be increased in this manner, little information is available in the literature related to the in vivo absorption pattern of drugs orally administered as PVP coprecipitates. Recently, however, it was demonstrated that both the rate and extent of absorption of the insoluble drug could be markedly enhanced when orally administered to rats in the form of a coprecipitate with PVP. The purpose of the present investigation was to ascertain the general appility of soluble polymer coprectation technique as a method for enhancing the in vitro dissolution rate of hydrophobic indomethacin. To accomplish this aim, the dissolution characteristics of pure indomethacin, indomethcin-polymer physical mixtures and indomethacin-polymer coprecipitates were quantitatively studied by comparing their relative dissolution rates. The solubility and dissolution behavior of these systems were also examined.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.723-735
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• 1998

Background : Vitamin C has been reported to have a role in the decrease of airway hyperresponsiveness in animal models. This data is based on some metabolic actions of vitamin C, such as promotion of histamine degradation, producing more $PGE_2$ than $PGF_{2\alpha}$ in cyclooxygenase pathway, decrease of smooth muscle contraction, and acting as reducing agent of oxidant. It has been also known that heavy smokers have lower blood levels of vitamin C than nonsmokers and this deficiency in heavy smokers have been explained by several mechanisms, such as increased oxidation by oxidants and free radicals, increased biosynthesis of catecholamine and serotonin released by nicotine, and inadequate dietary intake. In this study, We attempted to assess effect of vitamin C on bronchial hyperresponsiveness in heavy smokers who have bronchial hyperresponsiveness and role of vitamin C on bronchial hyperresponsiveness. Method: To assess acute effect of vitamin C on airway hyperresponsiveness, blood sample for vitamin C level and spirometry, methacholine challenge test were done in 17 smokers and 8 nonsmokers, and one hour after oral administration of vitamin C 3 g, blood sample for vitamin C level and spirometry, methacholine challenge test were repeated. To assess chronic effect of vitamin C on airway hyperresponsiveness, after daily administration of vitamin C 1 g for one week in 17 smokers, blood sample for vitamin C level and spirometry, methacholine challenge test were done. To assess role of vitamin C, after oral administration of vitamin C 3 g plus indomethacin 100 mg in 12 of 15 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were done and after oral intake of indomethacin 100 mg in 12 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were repeated. Result: There were no significant differences in whole blood vitamin C levels between smokers($1.17{\pm}0.22$ mg/dL) and nonsmcikers($1.14{\pm}0.19$ mg/dL) (p>0.05). Fifteen of the 17 smokers(88.2%) were reactive to methacholine challenge test and 10 of the 15 smokers who were reactive to methacholine challenge test were less than 8 mg/dL in $PC_{20}FEV-2$, and 7 of the 8 nonsmokers(87.5%) were nonreactive to methacholine challenge test There were significant decrease in bronchial responsiveness after oral administration of vitamin C 3 g in 13 of the 15 smokers who were reactive to methacholine challenge test This significant decrease persisted with maintenance daily administration of 1 g for one week. $PC_{20}FEV-2$ were not correlated to vitamin C levels in smokers. After oral administration of indomethacin 100 mg, significant reduction of bronchial responsiveness that occured after oral administration of vitamin C 3 g in smokers were attenuated. Conclusion: Although there were no significant differences in whole blood vitamin C levels between smokers and nonsmokers. heavy smokers have significant increase in bronchial responsiveness than nonsmokers. This bronchial hyperresponsiveness of heavy smokers can be attenuated by vitamin C supplement. Disappearance of vitamin C effect by indomethacin supplement may suggest that vitamin C exert its effect via alteration of arachidonic acid metabolism.

• The Journal of Korean Obstetrics and Gynecology
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• v.15 no.4
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• pp.45-60
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• 2002

Mouse calvarial osteoblast cells were isolated and cultured. To examine whether the cells produce active gelatinases in culture medium or not,the cells were analyzed using by zymograsphic analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). We show that mouse calvarial osteoblasts in culture constitutively synthesize progelatinase- A. Then, mouse osteoblasts, which were stimulated by PTH, $1,25(OH)_2D_3$, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agent's, showed increased collagenolysis by producing the active gelatinase. However, treatment of indomethacin and dexamethasone significantly decreased those effects of collagenolysis in mouse osteoblastic cells. On the other hand, IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, when it was examined the effects of indomethacin and dexamethasone on the dose dependent responses of $IL-1{\alpha}$, indomethacin and dexametasone produced a rightward shift in the IL-1 dose response curve. The results of in vitro cytotoxicities showed that Taeyoungjon-Jahage water extracts(T.Y.J-J.H.G extracts) have no any cytotoxicities in concentrations of $1-200\;{\mu}g/ml$ and furthermore there is no any cytotoxicity even in concentration of $300\;{\mu}g/ml$ on mouse calvarial bone cells. T.Y.J.-J.H.G. extracts had protective activity against PTH (2 units/mI), or MCM (5%, v/v), or $rhIL-1{\alpha}$ (1 ng/mI) or $1,25(OH)_2D3$ (10 ng/ml) , $IL-1{\alpha}$ and $IL-1{\beta}-induced$ collagenolysis in the mouse calvarial cells. Pretreatment of the T.Y.J.-J.H.G.extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore. the medicinal extracts were shown to have the protective effects against collagenolysis induced by $IL-1{\alpha}$ and $IL-1{\beta}$. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resortion agents of PTH, $1,25(OH)_2D_3$, $IL-1{\beta}$ and $IL-1{\alpha}$, with strong protective effect in pretreatment with the extracts. T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. The inhibition extent and phenomena of IL-1 stimulated bone resorption by nonsteroidal anti-inflammatory agents of indomethacin and dexamethasone were similar to those obtained by T.Y.J.-J.H.G. extracts treatment in the mouse calvarial tissue culture system. These results indicated that the T.Y.J.-J.H.G.-water extracts are highly stable and applicable to clinical uses in osteoporosis.

• 대한예방의학회:학술대회논문집
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• 1995.10a
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• pp.351-352
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• 1995

• Bulletin of the Korean Chemical Society
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• v.21 no.3
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• pp.361-363
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• 2000

• Archives of Pharmacal Research
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• v.15 no.3
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• pp.251-255
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• 1992

A number of 4-hydroxy-2H (or alkyl)-N-(3-aralkyl-2-thio-1-hydantoinyl)-1, 2-benzothiazine3-carboxamide 1, 1-dioxides were synthesized through the reaction of 4-hydroxy-2H (or alkyl)1, 2-benzothiazine-3-carboxylic methyl ester 1, 1-dioxide and 1-amino-2-thio-3-aralkyl-4-imidazolones in xylene. The compounds synthesized were screened for antinflammatory effect on carrageenin-induced edema in rat and for analgesic effect on acetic acid-induced Writhing syndrome in mice. Most compounds were inhibots of carrageenin-induced rat foot edema and some showed significant antinflammatory activity comparable to that of indomethacin and significant analgesic activity comparable to that of indomethacin and aspirin.

• Archives of Pharmacal Research
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• v.7 no.1
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• pp.33-40
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• 1984

In domethacin was microencapsulated with ethylcellulose using a modified spherical agglomeration process, aiming at a sustained release proparation without side effects on the stomach. The surface morphology of the microcapsules was examined using scanning electron microscopy. The microcapsules were porous and spherical, and their porosity increased with increasing the viscosity of ethylcellulose. In vitro dissolution process followed Higuchi's diffusion model for first 3 hr. Release rate of the drug from microcapsules decreased as the viscosity of ethylcellulose was decreased. The release rate also decreased with increasing the microcapsule size. The microcapsules induced less gastric ulcer in rats than raw drug.