• Journal of Radiation Protection and Research
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• 제26권4호
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• pp.367-374
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• 2001

방사선 조사가 흰쥐 식도에 미치는 영향과 sucralfate의 효과 여부를 알아보고자 하였다. 총 60마리의 흰쥐를 대상으로 정상대조군, sucralfate투여군, 10 Gy 와 20 Gy의 방사선 단독조사군, 10 Gy와 20 Gy의 방사선 조사-sucralfate병용군 등 여섯 군으로 구분하였다. 실험기간동안 흰쥐의 체중 변화의 조사와 함께 바륨-식도 조영술을 시행하였고, 방사선조사 후 3일, 7일, 14일 및 28일째에 얻은 식도에 나타난 병리조직학적 병변을 점수화하여 각 처리군을 비교관찰 하였다. 정상대조군은 10 Gy 와 20 Gy의 방사선 단독 조사군과 10 Gy 와 20 Gy의 방사선조사-sucralfate병용군에 비하여 체중 증가를 보였으나 (p=0.03, p=0.02, p=0.04, p=0.02), 이들 실험군들 사이에는 차이가 없었다. 10 Gy와 20 Gy의 방사선 단독조사군의 식도 조영술 소견은 7일째부터 식도 전장에 걸쳐 식도 내강이 좁아지고 경직성을 보였으며 10 Gy, 방사선조사-sucralfate병용군은 대조군과 유사한 소견을 보였다. 10 Gy와 20 Gy의 방사선 단독조사군에서 식도의 병리조직학적 손상등급은 정상군과 비교하여 매우 유의한 차이를 보였다 (p=0.03, p=0.008). 10 Gy 방사선 단독조사군과 10Gy 방사선조사-sucralfate병용군간의 손상등급은 방사선조사 후 3일 및 7일째까지 유의한 차이를 보였다( p=0.04, p=0.03 ), 본 연구에서 sucralfate는 한계선량이내에서 방사선조사시 흰쥐의 식도점막을 보호하는 데 도움이 됨을 확인하였다.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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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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• 제1권2호
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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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• 제2권2호
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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.

• 약학회지
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• 제37권4호
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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.

• 약학회지
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• 제37권5호
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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.

• 대한본초학회지
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• 제34권2호
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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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• 제20권4호
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• pp.343-352
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• 2002

목적 : 자궁경부암의 경우 종양에 충분한 양의 방사선을 조사하기 위해서는 직장도 고선량의 방사선을 받게 된다. 이로 인해 직장염을 비롯한 만성부작용이 발생하며 직장 출혈 빈도를 $5\~30\%$ 보고하고 있다. 저자는 완치 목적의 방사선치료를 받은 자궁경부암 환자들을 대상으로 직장 출혈 빈도와 그와 관련된 위험인자들을 분석하고 치료 방법을 살펴보고자 한다. 대상 및 방법 : 1994년 9월과 1999년 12월 사이에 방사선 단독치료를 받은 213명의 자궁경부암 환자를 대상으로 하였다. 90명이 외부 방사선치료의 일부를 하루 2회씩 받았다(변형된 다분할 방사선치료). 자궁주위조직의 외부 방사선량은 총 $51\~59\;Gy$였고 근접방사선치료로 A점에 총 $28\~30\;Gy$ (4 Gy씩 7회 혹은 5 Gy씩 6회)를 조사하였다. 직장에 조사된 선량은 ICRU 38에서 정한 위치와, 모의촬영필름에서 바리움에 의해 구분되는 직장 앞쪽 벽의 한 점을 선정하여 계산하였다. 직장출혈의 정도는 LENT/SOMA에 따라 분류하였다. 추적관찰 기간은 $12\~86$개월(중앙값 39개월)이었다. 결과 : 27명$(12.7\%)$의 환자에서 직장출혈이 발생하였다(등급 2와 3:각각 16명과 2명, $8.5\%$). 이들 중에서 추적관찰 기간동안 질-직장루 또는 폐쇄로 진행된 경우는 없었다 발생시기는 대부분의 환자에서$(92.6\%)$ 치료 종료 후 2년 이내였다(중앙값 16개월). 단변량분석에서 위험인자로 icruCRBED (직장이 받은 총 생물학적 동등선량), 자궁주위조직의 방사선량, 및 병기였다. icruCRBED가 100 미만인 경우와 100 이상인 경우 $4.2\%$ 대 $19.7\%$, 자궁주위조직에 대한 조사선량 55 Gy 미만과 그 이상인 경우가 $5.1\%$ 대 $22.1\%$, 병기 II 이하인 경우와 III 이상인 경우가 $10.5\%$ 대 $31.8\%$였다. 다변량분석에서는 icruCREED 만이 유의하였다(0=0.0432). 등급 1 출혈은 자연적으로 소실되거나(3명) $1\~2$개월의 sucralfate 관장으로 멈추었다. 등급 2의 환자 6명은 $1\~2$개월 동안 sucralfate 관장으로 출혈의 빈도와 양이 줄어들었고 이 중 4명은 전기응고술을 추가로 시행하였다. 다른 9명은 전기응고술을 먼저 시행하였다(4명; sucralfate 관장 병행). 모두 $3\~10$개월 내에 정지되었다. 등급 3의 출혈은 잦은 전기응고술과 수혈을 요하였다. 결론 : 본 연구에서 중등도 이상의 직장출혈빈도가 $8.5\%$로 타 문헌에서 보고된 빈도와 유사한 결과였다. 직장에 조사된 총 생물학적 동등선량이 100 Gy 이상인 경우에 직장출혈이 유의하게 증가하므로, 치료계획시 생물학적 동등선량을 고려함으로써 휴유증 감소에 도움이 될 것으로 생각된다. 직장출혈이 발생한 환자에서 조기에 적극적으로 치료를 시행함으로써 출혈로 인한 불편함을 신속하게 해결하고 이로 인한 심리적 불안감을 해소할 수 있으며 나아가 삶의 질 향상에도 도움을 줄 수 있을 것으로 판단된다.

• Journal of Pharmaceutical Investigation
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• 제28권2호
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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.