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흰쥐에서 Ursodeoxycholic Acid 및 Silymarin을 함유한 의약조성물(DWP305)의 연용투여에 의한 간내 담즙산 조성변화
조재열(Jae Youl Cho),연제덕(Je Deuk Yeon),남권호(Kweon Ho Nam),김점용(Jeum Yong Kim),유은숙(Eun Sook Yoo),유영효(Young Hyo Yu),박명환(Myung Hwan Park) 대한약학회 1996 약학회지 Vol.40 No.3
DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins (B1 and B2), is a drug currently being developed for hepatic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there''s no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.
랫트에 있어서 DWH-01(Ranitidine : Bismuth subcitrate : Sucralfate)의 아급성독성에 관한 연구
박선미(Sun Mee Park),김형식(Hyung Sik Kim),김용기(Yong Kee Kim),변수현(Soo Hyun Byung),연제덕(Je Deuk Yeon),유영효(Young Hyo Yu),이병무(Byung Mu Lee),이향우(Hyang Woo Lee) 대한약학회 1993 약학회지 Vol.37 No.4
Subacute toxicities of DWH-01(Ranitidine : Bismuth : Sucralfate = 1.5 : 2 : 6) were inverstigated in Sprague-Dawley rats. After oral administration of DWH-01 with different dosages of 5g/kg, lg/kg, and 0.2g/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.
랫드에서 l-muscone의 급성독성 및 아급성독성시험 연구
오승민,연제덕,남혜운,박대규,조명행,정규혁 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gavaged with l-muscone of two doses(0, 5.0g/㎏). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0g/㎏. Therefore, oral LD_50 of l-muscone was consider to be higher than 5.0g/㎏ in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3,000 ㎎/㎏. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal LD_50 of l-muscone were 1,920 ㎎/㎏ in male and female rats. In the subacute study. l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 ㎎/㎏). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysis, and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 ㎎/㎏/day in this study.
오승민,남혜윤,김준수,연제덕,신대희,이진영,박대규,조명행,정규혁 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
The acute and subacute toxicity of New Woohwangchungsimwon(NWCH) which was used l-muscone as substitutive material of musk were investigated in S.D. rats. In intraperitoneal acute toxicity test, rats(Sprague-Dawley, SPF) were injected intraperitoneally with dosages of 0, 540, 750, 1,070, 1,500 and 3,000 ㎎/㎏. Body weights were significantly decreased at 540 ㎎/㎏ dose group in both sexes and abnormal autopsy findings were founded in both sexes at all treated groups. Intraperitoneal LD_50 of NWCH was 812.3 ㎎/㎏ in male and 872.3 ㎎/㎏ in female rats. In the subacute toxicity study, NWCH was administrated orally to both sexes of rats for 4 weeks as several doses(0, 320, 800 and 2,000 ㎎/㎏). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysis, and other findings. Above data strongly suggest that no observed adverse effect level of NWCH might be over 2,000 ㎎/㎏/day in this study.