• Journal of Radiation Protection and Research
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• v.26 no.4
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• pp.367-374
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• 2001

The study was designed to evaluate the response of sucralfate against the esophageal damage of rat by irradiation. Sixty Sprague-Dawley rats weighing 200-250 gm were divided into six groups including only sucralfate group, the group of 10 Gy or 20 Gy radiation alone, the groups of 10 Gy or 20 Gy radiation-sucralfate combination, and control. Each group was sacrificed at 3, 7, 14, and 28 days after irradiation. For evaluation of the radiation-induced esophageal lesions, there were examined the change of body weight, barium-esophagogram and histopathologic findings. Mean body weight gain was decreased in the groups with 10 Gy or 20 Gy radiation alone and 10 Gy or 20 Gy radiation-sucralfate combination as comparing with control (p=0.03, p=0.02, p=0.04, p=0.02), but there was no difference between the groups of 10 Gy or 20 Gy radiation alone and the groups of 10 Gy or 20 Gy radiation-sucralfate combination. In the 10 Gy and 20 Gy radiation alone groups, barium esophagograms showed diffuse narrowing and stiffness through the entire esophagus from 7 days after irradiation, but there was similar pattern of esophagograms between the groups of 10 Gy radiation-sucralfate combination and the control. Histopathoiogic lesion scores of 10 Gy and 20 Gy radiation groups were significantly higher than the control (p=0.03, p=0.008). In the 10 Gy radiation group, there were significantly higher lesion scores at 3 and 7 days after irradiation as comparing with those in the group of radiation-sucralfate combination (p=0.04, p=0.03). These results suggest that sucralfate might be played as a role of protection from acute radiation-induced esophagitis within the limit of tolerable radiation doses.

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.331-338
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• 1995

In order to screen appropriate preservatives for the suspension containing sucralfate, neusilin and hydrotalcite, the patterns and mechanism of the adsorption and desorption of several preservatives on these antacids were studied. The employed preservatives were parabens(methyl, propyl, butyl), chlorhexidine diacetate and sorbic acid. While none of parabens were adsorbed on three antacids, chlorhexidine diacetate was strongly adsorbed on all the antacids employed, especially on hydrotalcite. Sorbic acid was not adsorbed on neusilin and hydrotalcite, however, 65% of sorbic acid was adsorbed on sucralfate. The adsorption of chlorhexidine diacetate on neusilin and hydrotalcite was partly physical and partly chemical, while its adsorption on sucralfate was almost chemical. Sorbic acid was completely deserted from sucralfate. In all cases, the adsorption isotherms were fitted well to both Freundlich equation and Langmuir equation. Based on these results, parabens and sorbic acid were the preservatives of choice for the suspension containing sucralfate, neusilin and hydrotalcite.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.93-93
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• 1995

The three combined products were prepared as suspended solutions composed of various ratio of Sucralfate, Hydrotalcite and Neusilin, into which 30% ethanol extracts of Machili cortex, and of Atractylodis rhizoma were added. The efficacy for these products was examined in vivo using a pyrous ligation method in rats. The influence of these products on the intestinal motility was also examined in mice. In all experimental setting, the antisecretory effect of the combined treatment was more pronounced than that of each drug alone. The combined treatment consisted of Sucralfate, Hydrotalcite, Neusilin ratios of 2:2:1 produced the highest inhibitory effect for the gastric secretion. The intestinal motility was not influenced significantly by the treatment of all experimental setting. The above results revealed that the therapeutic dose of Sucralfate, Hydrotalcite, Neusilin given in combination showed a synergistic effect for the inhibition of gastric secretion and little side effect on the intestinal motility. Therefore, the combined product with Sucralfate, Hydrotalcite, Neusilin ratio of 2:2:1 is recommended for the useful drug to heal the gastrointestinal diseases with no side effect on the intestinal motility.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.262-265
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• 1993

Acute toxicities of DWH-01 (Ranitidine : Bismuth : Sucralfate= 1.5: 2 : 6) were investigated in Sprague-Dawley rats. Seven days after oral administration of DWH-01 with different doses (10 g/kg, 5 g/kg, 2.5 g/kg, 1.25 g/kg, 0.625 g/kg), we examined numbers of deaths, general signs, weight measurement and histopathological examination for both sexes of rats. Summaried results are: 1) No deaths were occurred, 2) There were no pathological and clinical differences compared with control group, 3) No significant changes of body weights were observed, and 4) In histopathological examinations of organs and tissues, there was some hemorrhage in a lung tissue of low dose group for male and female respectively, but it was thought to be caused by environmental factor. The results suggest that toxicity of DWH-01 is low and its $LD_{50}$ is over 10 g/kg in Sprague-Dawley rats.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.185-189
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• 1994

The eight combined products composed of ranitidine.HCI, tripotassium dicitrato bismuthate and sucralfate were prepared with various ratios and studied in therapeutic effects of them on various gastrointestinal diseases. These were induced in rats with the porous ligation, ethanol-HCI, acetic acid and cysteamine method, etc. In all experimental setting, the effect of the combined treating was more pronounced than the effect of each drug alone. Specially, the combined treatment consisted of ranitidine : tripotassium dicitrato bismuthate sucralfate ratio of 1.5 : 2 : 6 showed the most powerful therapeutic effect on acute gastric ulcer model and revealed a significant acceleration of the healing on chronic gastroduodenal ulcer model. And that, therapeutic doses of ranitidine, tripotassium dicitrato bismuthate arid sucralfate given in combination had an additive or, in some case, synergistic effect. From the above results, this combined treatment may useful to heal the gastrointestinal diseases that aren't cured well by treatment of each them alone.

• YAKHAK HOEJI
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• v.37 no.4
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• pp.408-419
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• 1993

Subacute toxicities of DWH-Ol(Ranitidine : Bismuth : Sucralfate=1.5:2:6) were inverstigated in Sprague-Dawley rats. After oral administration of DWH-01 with different dosages of 5 g/kg, l g/kg, and 0.2 g/kg, we examined the number of deaths, general signs, food intake, water intake, body weight and histopatholgical changes for both sexes of rats. During the adminstration period, urinalysis and opthalmological examination were also performed in the treated animals. 1) Animals were all survived for 4 weeks. 2) There were no significant differences in pathological and opthalmological findings between the control and treated animals. 3) There were no significant changes in body weight, food intake and water intake compared with control group. 4) In hematological examination and blood chemical analysis, there was no significant change compared with control group. 5) In histopathological examinations of organs and tissues, there was some hemorrhage in a lung tissue of low dose group, but it was thought to be caused by environmental factor. These data suggest that DWH-01 is not subacutely toxic in Sprague-Dawley rats.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.544-548
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• 1993

The pharmacokinetics of DWP302, a new combined ranitidine preparation in rats and dogs was studied using HPLC. DWP302 was composed of ranitidine, sucralfate and tripotassium dicitrato bismuthate. Especially, this study was focused on the possibilities that the concomitant administration of either sucralfate or TDB may affect the absorption of orally administered ranitidine. Ranitidine and DWP302 were orally administered to rats at a dose of ranitidine 10mg/kg. Several rats showed the biphasic peak of plasma concentration. AUC$_{S_{0-8}}$ of ranitidine and DWP302 group were found to be 1040$\pm$109 and 945$\pm$124 ng.hr/ml, respectively, and there was no significant difference between both AUCs. In a cross-over study for dogs, $C_{max}$, t$_{1/2}$ beta and total AUC of ranitidine group were found to be 625.8$\pm$86.7 ng/ml, 2.80$\pm$0.28 hr and 1688$\pm$127 ng.hr/ml, and those of DWP302 group were 562.6$\pm$120.9 ng/ml, 3.05$\pm$0.30 hr and 1673$\pm$123 ng.hr/ml, respectively. There was no significant difference between those parameters, but Tmax of DWP302 group (1.69$\pm$0.31 hr) was significantly different from ranitidine group (1.13$\pm$0.26 hr). The results suggest that either sucralfate or TDB may affect the lag-time or rate of absorption of ranitidine but not the extent of absorption.

• The Korea Journal of Herbology
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• v.34 no.2
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• pp.1-14
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• 2019

Objective : This study was designed to evaluate the protective effect of Rehmanniae Radix Crudus (RC) in 150 mM HCl/ethanol induced acute gastritis mice. Methods : ICR mice were divided into 5 groups (normal group, control group, 10 mg/kg sucralfate treated group, 50 mg/kg RC treated group, 100 mg/kg RC treated group, n=8). Normal group was not take any treatment. Control group induced gastritis 1 hour after ingestion of distilled water. 10 mg/kg sucralfate induced group was induced gastritis 1 hour after ingestion of distilled of sucralfate 10 mg/kg. 50 mg/kg and 100 mg/kg RC treated groups were induced gastritis 1 hour after ingestion of distilled of RC 50 mg/kg and 100 mg/kg. After 1 hour of gastritis induction, removed the stomach tissue. We examined histological observations, oxidative stress biomarkers, antioxidant proteins, inflammatory mediators and cytokines. Results : In this study, the RC treatment group showed gastritis and gastric ulcer inhibition, and the area of injury decreased. The oxidative stress biomarkers such as reactive oxygen species (ROS) and peroxy nitrite ($ONOO^-$) in the serum were reduced in the RC treated group. Inaddition, antioxidant proteins (nuclear factor erythroid 2-related factor 2, Heme oxygenase 1) were increased in RC treated group, and the expression of inflammatory mediators and cytokines induced by nuclear factor-kappa B activation was inhibited. Conclusion : According to the results, RC may have an excellent inhibitory effect on acute gastritis and gastric ulcer.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.343-352
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• 2002

Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.99-107
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• 1998

The objective of this study was to develop effective oral formulations of rhEGF for gastric ulcer healing using polycarbophil. hydroxypropylcellulose(HPC) and sucralfate as its bioadhesive bases. Cytoprotective effects of rhEGF, cell proliferation and differentiation. on the ulcers induced by ethanol or acetic acid in rats were studied. rhEGF release from HPC formulation was much faster than that from polycarbophil formulation. HPC formulation combined with small amount of sucralfate showed much slower release of rhEGF than only HPC base only. rhEGF preparations with bioadhesive polymers showed better effects on the healing of gastric ulcers than EGF solution when administered orally. When rhEGF preparations were administered at once and the animals were under starvation, polycarbophil formulation showed better effect on gastric ulcers than HPC formulation. Otherwise, when rhEGF preparations were given more than three times and the rats were fed normally, HPC formulation showed good healing efficacy of ulcers compared to polycarbophil formulation. rhEGF showed dose-dependent effect on the healing of both chronic and acute ulcers.