• Toxicological Research
• /
• v.16 no.2
• /
• pp.151-161
• /
• 2000

The Three months subacute toxicity of water soluble dimethyl dimethoxy biphenylate derivative (DDB-S), newly formulated therapeutic agent for hepatitis, was invesgated in SD rats. The body weight and clinical signs were observed after intravenous injection of DDBs at doses of 57, 75 and 100 mg/kg/day for three months. Decrease in motor activity and tremor were observed above 75mg/kg treated groups. Statistically significant changes at serum biochemical analysis were found in some group, how-ever, those changes were within the normal range and had no relationship with dosage. There was no abnormal morphological and pathological findings in relation to DDB-S treatment. The no observable adverse effect level of DDB-S in rats was estimated to be 57 mg/kg/day in this study.

• Toxicological Research
• /
• v.13 no.4
• /
• pp.423-433
• /
• 1997

The acute and subacute toxicity of water soluble dimethyl dimethoxy biphenylate derivative (new DDB), hepatitis therapeutics, were investigated in SD rats. In the acute toxicity study, body weights and clinical signs were observed for 7 days after the intravenous injection of new DDB at doses of 140, 182, 236, 307 and 400 mg/kg(r=1.3). Death. Severe convulsion, tremor and decrease motor activity were observed in almost treated groups (except the 140 mg/kg treated group). Changes of body weight in treated groups were not significantly different from control group. Autopsy of survived animals revealed no abnormal gross findings related to new DDB. As a results, the $LD_{50}$ values of new DDB were 244.1 mg/kg for male and 232.5 mg/kg for female. In subacute toxicity study, body weights and clinical signs were observed after intravenous injection of new DDB at doses of 57, 75 and 100 mg/kg/day for 28 days. Death, decrease motor activity and tremor were observed above 75 mg/kg treated groups. Statistically significant changes were observed in hematological and biochemical parameters of new DDB-treated groups; however, these changes were within normal range and had no relationship with dosage. Several abnormal findings were observed in microscopic examination of tissue; however, these findings were not caused by new DDB but environmental factor. The no toxic dose level of new DDB were estimated to be 57 mg/kg/day in this study.

• Toxicological Research
• /
• v.14 no.3
• /
• pp.307-313
• /
• 1998

Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.

• Toxicological Research
• /
• v.16 no.3
• /
• pp.239-253
• /
• 2000

This study was carried out to evaluate the three months subacute intravenous toxicity of water soluble dimethyl dimethoxy biphenylate derivative (DDB-S), a newly formulated therapeutic agent for hepatitis, in Beagle dogs. Groups of 12 male and 12 female dogs were given different dosage of DDB-S, 10 mg/kg/day (high dose group), 5 mg/kg/day (middle dose group), 2.5 mg/kg/day (low dose group) and 0 mg/kg/day (control group) for three months by intravenous route. 1n the three months intravenous toxicity study, there were neither dead animals nor significant changes of body weights during the experimental period. 1n addition to, no significant DDB-S related changes were found in clinical signs, urinalysis and other findings. Statistical changes were observed in hematological. biochemical, partial thromboplastin time (PIT) and organ weight parameters of treated groups. However, these alteration had no relationship with dosage. No histopathological lesions were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in Beagle dogs might be over 10 mg/kg/day in this study.

• Journal of Pharmaceutical Investigation
• /
• v.27 no.3
• /
• pp.173-179
• /
• 1997

A water-soluble DDB derivative (Bis{2-(methylamino)ethyl}-4,4-dimethoxy-5,5',6,6'-dimethylenedioxy-biphenyl-2,2'-dicarboxylate, DDB-S) was synthesized and its therapeutic effects on the liver damage induced by carbon tetrachloride in rats were evaluated. Oral administration of DDB-S reduced the aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities and increased total protein and albumin contents in the serum of the carbon tetrachloride intoxicated rat. Therapeutic effects of DDB-S by intravenous injection was also investigated using carbon tetrachloride intoxicated rats. Histological studies showed that IV injection of DDB-S had improved the typical necrosis around centrilobular area in liver tissue due to the carbon tetrachloride intoxication and also prevented the elevation of liver weigh/body weight ratio. IV administration of DDB-S to $CCl_4-treated$ rats significantly decreased AST & ALT activities and also prevented the decrease of aniline hydroxylation activity of the liver. These results indicate that i.v. administration of DDB-S is very effective in recovering the liver function in $CCl_4-treated$ rats.