• YAKHAK HOEJI
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• v.35 no.5
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• pp.372-378
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• 1991

To increase the stability and bioavailability of Omeprazole(OMP), which is used newly as a proton-pump inhibitor, inclusion complex of OMP with $\beta$-cyclodextrin($\beta$-CD) was prepared by coprecipitation method and its characteristics were ascertained by means of solubility test, DSC, IR, and the accelerated stability analysis. The type of OMP inclusion complex is classified as Bs-type on phase solubility diagram, and the stoichiometric ratio of OMP: $\beta$-CD complex is 1:2 and formation constant is 80.82/mole. The solubility of the complex could be increased remarkably by complexation compare with OMP. Degradation process of both OMP and OMP complex followed apparent first-order kinetics, of which degradation rate constants and activation energies are k$_{25}$=8.1$\times$10$^{-4}$/day, E$_{a}$=22 Kcal/mole (OMP), and k$_{25}$=4.65$\times$10$^{-6}$/day, E$_{a}$=35 Kcal/mole (complex), respectively. These results show the increase of the stability and solubility of OMP markedly, therefore it is believed that the improvement of stabilization for OMP by inclusion complexation might be practically available.

• Journal of Pharmaceutical Investigation
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• v.25 no.1
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• pp.9-17
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• 1995

To stabilize omeprazole(OMP), ethylenediamine(ED) complex of omeprazole(OMPED) was prepared by reaction between OMP and ED in methanol, and the complex formation was confirmed by the instrumental analysis, i.e., IR, DSC, EA, NMR, MS and XRD. The rates of decomposition of OMP and OMPED in aqueous solution and the shelf lives at standard temperature were measured by accelerated stability analysis. The results are summarized as follows; The mole ratio of OMP and ED in OMPED complex is 1:1, the energy of formation within OMPED might be combined between polar imidazole group of OMP with induced a dipole amine group in the readily polarizable ED molecule. At standard temperature the degradation rate constant of OMP in aqueous solution is $2.540{\times}10^{-2}\;hr^{-1}$ and the shelf life is 4.15 hrs, and in the case of OMPED the degradation rate constant is $7.986{\times}10^{-4}\;hr^{-1}$ and the shelf life is 131.96 hrs. So, the OMPED has about 31 times longer shelf life than OMP. The activation energy of OMP and OMPED are 5.23 and 18.55 kcal $mole^{-1}$ respectively. The stability of OMP is dependent chiefly on pH in the solutions and it decomposes readily in acidic medium by hydrogen ion catalized reaction but becomes stable beyond pH 9.0. In case of the ED-complex, OMPED is stable in neutral as well as in dilute acidic solutions even in pH 6, OMPED is very stable to light(UV), that is, the rate constant and shelf life of OMP are $k=1.0188{\times}10^{-2}\;day^{-1}$, $T_{90%}=4.5 \;days$, on the other hand, the those of OMPED are $k=7.138{\times}10^{-4}\;day^{-1}$, $T_{90%}=64.1\;days$, respectively. From the above results, it is thought that new dosage forms could be developed by using the OMPED as a potential OMP complex.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.128-141
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• 2010

Purpose : The object of this study was to observe the suppressive effects of Yijintang-gamibang (YJGMB), Yijintang with Atractylodis Rhizoma, Massa Medicata Fermentata, Hordei Fructus Germiniatus, and Coptidis Rhizoma. YJGMB has been traditionally used in Korean medicine for treating various digestive diseases. We tested it on the rat reflux esophagitis (RE) induced by pylorus and forestomach ligation in rats as compared with omeprazole, a well-known proton pump inhibitor. Method : Three different dosages of YJGMB 200, 100 and 50mg/kg, were orally pretreated once a day for 28 days before pylorus and forestomach ligation. Seven groups, each of 8 rats per group were used in the study. Six hours after pylorus and forestomach ligation, changes of the stomach and esophagus lesion areas, gastric volumes, acid and pepsin outputs, invasive lesion percentages, fundic mucosa and total thicknesses were measured as histomorphometry. The results were compared with omeprazole, antioxidant and proton pump inhibitor, and 30 and 10mg/kg treated groups in which the effects on RE were already confirmed. Results : As results of pylorus and forestomach ligation, marked increases of esophageal and gastric mucosa lesion areas, gastric volumes, acid outputs, pepsin outputs were observed with histopathological changes of RE, such as hemorrhages, ulcerative lesions and edematous changes on the fundic mucosa. However, these pylorus and forestomach ligation-induced RE were dose-dependently inhibited by treatment of 200, 100 and 50mg/kg of YJGMB. YJGMB 200mg/kg showed similar protective effects as compared with 30mg/kg of omeprazole in the present study, and more favorable effects were observed in 50mg/kg of YJGMB treated rats as compared with omeprazole 10mg/kg in the present study. Conclusion : The results obtained in this study suggest that YJGMB has favorable protective effects on the RE induced by pylorus and forestomach ligation. Therefore, it is expected that YJGMB will also show favorable effects on RE corresponding well to the suggestion of traditional Korean medicine. However, more detailed mechanism studies should be conducted in future with the screening of the biological active chemical compounds in herbs.

• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.41-49
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• 1993

The bioequivalence of two omeprazole enteric-coated products was evaluated in 16 normal male volunteers (age 26-32 yr, body weight 57-75 kg) following single oral administration. Test product was enteric-coated KD-182 tablet (Chong Kun Dang Corp., Korea) and reference product was $Rosec^{\circledR}$ capsule containing enteric-coated pellets of omeprazole (Yuhan Corp., Korea). Both products contain 20 mg of omeprazole. One tablet or capsule of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study ($2\;{\times}\;2$ Latin square method). Average drug concetrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products(p>0.05); the area under the concentrationtime curve to last sampling time (8 hr) $(AUC_{0-8hr})$ $(1946.5{\pm}675.3\;vs\;2018.3{\pm}761.6\;ng{\cdot}hr/ml)$, AUC from time zero to infinite $(AUC_{o-\infty})$ $(2288.6{\pm}1212.8\;vs\;2264.9{\pm}1001.3\;ng{\cdot}hr/ml)$, maximum plasma concentration $(C_{max})$ $(772.5{\pm}283.3\;vs\;925.8{\pm}187.7\;ng/ml)$, time to maximum plasma concentration $(T_{max})$ $(2.38{\pm}1.06\;vs\;2.34{\pm}1.09\;hr)$, apparent elimination rate constant $(k_{\ell})$ $(0.5339{\pm}0.2687\;vs\;0.5769 {\pm}0.2184\;hr^{-I})$, apparent absorption rate constant $(k_a)$ $(1.1536{\pm}0.5278\;vs\;0.9739{\pm}0.9507 hr^{-1})$ and mean residence time (MRT) $(3.13{\pm}0.73\;vs \;3.41{\pm}1.04\;hr)$. The differences of mean $(AUC_{0-8hr})$, $C_{max}$, $T_{max}$ and MRT between the two products (3.69, 19.83, 1.32 and 8.99%, respectively) were less than 20%. The power $(1-{\beta})$ and treatment difference $(\triangle)$ for $AUC_{o-8hr}$ $C_{max}$ and MRT were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different each other(p>0.05). These results suggest that the bioavailability of KD-182 tablet is not significantly different from that of $Rosec^{\circledR}$ capsule. Therefore, two products are bioequivalent based on the current results.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.1
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• pp.12-20
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• 2005

Purpose: Helicobacter pylori infection is known to be associated with acute or chronic abdominal pain and upper gastrointestinal bleeding in children. This study was performed to analyze the gastroduodenoscopic findings and the efficacy of triple therapy with omeprazole, amoxicillin and clarithromycin between one and two weeks of duration in children with H. pylori infection. Methods: We have assessed retrospectively 60 patients presented with acute or chronic abdominal pain or upper gastrointestinal bleeding. H. pylori infection was confirmed by endoscopic biopsy and rapid urease test. Out of 60 patients, 30 patients were treated with a combination of omeprazole, amoxicillin, and clarithromycin for one week, and the other 30 patients were treated for two weeks with the same medication. Efficacy of treatment was assessed 4 weeks after the termination of treatment by using the $^{13}C$ urea breath test. Results: The 60 patients with the complaint of diffuse abdominal pain, epigastric pain, vomiting or hematemesis were included in this study. One-week treatment group (group I) consisted of 30 patients (14 male, 16 female) with mean age of $11.6{\pm}2.67years$. Two-week treatment group (group II) consisted of 30 patients (11 male, 19 female) with mean age of $10.7{\pm}4.17years$. In group I, H pylori were eradicated in 26 out of 30 patients (86.7%). In group II, H. pylori were eradicated in 26 out of 30 children (86.7%). Both groups did $^{13}C$ urea breath test after 4 weeks after termination of the triple therapy. The eradication rates were same in both groups as 86.7%, 26 out of 30 patients in each group. The results of endoscopy were nodular gastritis 26 (43.3%), erosive gastritis 10 (16.7%), hemorrhagic gastritis 7 (11.7%), gastric ulcer 2 (3.3%) and normal finding 15 (25.0%). Conclusion: In this study, the nodular gastritis was most common endoscopic findings with H. pylori positive patients. The eradication rate of H. pylori with omeprazole, amoxicillin and clarithromycin was 86.7% and it would be highly effective as primary treatment with no significant differences in the eradication rate between one-week and two-week treatment groups. However, we should need more long-term follow-up data.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.278.3-279
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• 2000

• The Journal of the Korean Society for Microbiology
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• v.34 no.6
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• pp.543-554
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• 1999

The purpose of this study was to evaluate the existence of amoxicillin, clarithromycin, and metronidazole resistance Helicobacter pylori and to determine the in-vitro MIC of two and three kinds of antibiotic concominant administration in the isolates. The antimicrobial agents tested against 169 H. pylori included metronidazole, amoxicillin, ciprofloxacin, clarithromycin, omeprazole, josamycin, erythromycin, and tetracycline. MIC of each antimicrobial agents was determined by broth microdilution method. The 169 strains of H. pylori were isolated from biopsy specimens of patients with gastric cancer. $MIC_{50}$ of clarithromycin, amoxicillin, metronidazole, omeprazole, erythromycin, josamycin, tetracycline, and ciprofloxacin was 2.0, 1.0, 4.0, 8.0, 0.5, 0.5, and $0.5\;{\mu}g/ml$, respectively. $MIC_{90}$ of clarithromycin, amoxicillin, metronidazole, omeprazole, erythromycin, josamycin, tetracycline, and ciprofloxacin was 64.0, 64.0, 32.0, 16.0, 8.0, 2.0, and $1.0\;{\mu}g/ml$, respectively. H. pylori isolates were detected in the following resistaince rates: 34.3% to clarithromycin, 31.9% to metronidazole, 20.7% to amoxicillin, 12.4% to erythromycin, and 10.1% to josamycin. The prevalence of the antibiotic resistant strains of H. pylori were detected 18.1% for two kind of antibiotics and 9.6% for three kind of antibiotics, and 3.9% for four kind of antibiotics. The $MIC_{90}$ of clarithromycin-, metronidazole-, and amoxicillin-resistant H. pylori was decreased under the $1\;{\mu}g/ml$ by the two or three kind of antibiotic concomitant administration in-vitro. These results suggest that two or three antibiotics concomitant administration could be more effective for the treatment of clarithromycin-, amoxicillin-, metronidazole-, and josamycin-resistant H. pylori strains.

• Journal of Microbiology and Biotechnology
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• v.9 no.3
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• pp.235-242
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• 1999

We investigated the growth-inhibitory mechanism of Helicobacter pylori by omeprazole (OMP) and its activated sulfenamide (OAS). Using dithiothreitol (DTT) and 5,5'-dithio-bis[2-nitrobenzoic acid] (DTNB; Ellman's reagent), we first determined the relationship between the binding capacity of these compounds to H. pylori membrane and its significance to membrane P-type ATPase activity. After incubation of the intact H. pylori cells with either OMP or OAS, the residual quantity of free SH-groups on the cell membrane was measured, and, the resulting values were plotted as a function of time. From this experiment, we found that there was a considerable difference in the membrane-binding rates between OMP and OAS. At neutral pH, the disulfide bond formation on H. pylori membrane was completed within 2 min of incubation of the intact cells with OAS. By OMP, however, it was gradually formed, exceeding 10 min of incubation for completion, whereby, the extent of P-type ATPase inhibition appeared to be proportional to the disulfide forming rate. From this data, it was suggested that the disulfide formation might directly affect enzyme activity. Since OMP per se cannot yield a disulfide bond with cysteine, it is predicted that the enzyme inactivation must be caused by the OAS form. Accordingly, we postulated that, under the neutral pH, OMP could be converted to OAS in the course of transport. By extrapolating the inhibitory slopes, we could evaluate K₁ values, relating to their minimal inhibitory concentrations (MICs) for H. pylori growth. In these MIC ranges, H. pylori uptake or vesicular export of nutrients such as peptides were totally prohibited, but their effect in Escherichia coli were negligible. From these observations, we strongly suggest that the P-type ATPase activity is essential for the survival of H. pylori cells in particular.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1153-1159
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• 2013

A novel solid-contact indium(III)-selective sensor based on bis-(1H-benzimidazole-5-methoxy-2-[(4-methoxy-3, 5-dimethyl-1-pyridinyl) 2-methyl]) thiosulfinate, known as an omeprazole dimer (OD) and a neutral ionophore, was constructed, and its performance characteristics were evaluated. The sensor was prepared by applying a membrane cocktail containing the ionophore to a graphite rod pre-coated with polyethylene dioxythiophene (PEDOT) conducting polymer as the ion-to-electron transducer. The membrane contained 3.6% OD, 2.3% oleic acid (OA) and 62% dioctyl phthalate (DOP) as the solvent mediator in PVC and produced a good potentiometric response to indium(III) ions with a Nernstian slope of 19.09 mV/decade. The constructed sensor possessed a linear concentration range from $3{\times}10^{-7}$ to $1{\times}10^{-2}$ M and a lower detection limit (LDL) of $1{\times}10^{-7}$ M indium(III) over a pH range of 4.0-7.0. It also displayed a fast response time and good selectivity for indium(III) over several other ions. The sensor can be used for longer than three months without any considerable divergence in potential. The sensor was utilized for direct and flow injection potentiometric (FIP) determination of indium(III) in alloys. The parameters that control the flow injection method were optimized. Indium(III) was quantitatively recovered, and the results agreed with those obtained using atomic absorption spectrophotometry, as confirmed by the f and t values. The sensor was also utilized as an indicator electrode for the potentiometric titration of fluoride in the presence of chloride, bromide, iodide and thiocyanate ions using indium(III) nitrate as the titrant.

• Archives of Pharmacal Research
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• v.29 no.6
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• pp.484-489
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• 2006

This Study evaluated the inhibitory action of $luteolin-7-O-{\beta}-D-glucuronopyranoside$, luteolin which was isolated from Salix gilgiana leaves, and omeprazole on reflux esophagitis and gastritis in rats. Reflux esophagitis and gastritis were induced surgically and by the administration of indomethacin, respectively. The intraduodenal administration of $luteolin-7-O-{\beta}-D-glucuronopyranoside$ decreased the ulcer index, injury area, gastric volume and acid output, and increased the gastric pH compared with luteolin. $Luteolin-7-O-{\beta}-D-glucuronopyranoside$ significantly decreased the size of the gastric lesions that had been induced by exposing the gastric mucosa to indomethacin. The malondialdehyde content, which is the end product of lipid peroxidation, was increased significantly after inducing of reflux esophagitis. The malondialdehyde content was decreased by $Luteolin-7-O-{\beta}-D-glucuronopyranoside$ but not luteolin or omeprazole. $Luteolin-7-O-{\beta}-D-glucuronopyranoside$ has a more potent antioxidative effect than luteolin. $Luteolin-7-O-{\beta}-D-glucuronopyranoside$ is a promising drug for the treatment of reflux esophagitis and gastritis.