• Archives of Pharmacal Research
• /
• 제8권3호
• /
• pp.99-107
• /
• 1985

The interaction of reduced riboflavin 2', 3', 4', 5'-tetrabutyrate with salicylic acid, aspirin, and salicylamide has been spectroscopically investigated to determine the binding mechanism. Hydrogen-1 and carbon-13 unclear magnetic resonance, infrared, and absoption spectra were measured in chloform-d and chloroform. The association of the reduced riboflavin with salicylic acid derivatives is different from that osidizd one. Salicylic acid and the reduced riboflavin form a cyclic hydrogen bounded complex through the imino (3-N, 5-N) protons and the carbonyl (2-C, 4-C) oxygens of the isolloxazine ring of the latter, and the carboxylic hydroxyl proton and carbonyl oxygen of the former. Aspirin and the reduced riboflavin form a complex by the same mode as salicylic acid. Salicylamide forms a cyclic hydrogen bonded complex with the reduced riboflavin through the imino (3-N, 5-N) protons and the carbonyl (2-C, 4-C) oxygens of the isoalloxazine ring, and the amino proton and the carbonyl oxygen of salic aylmide. It appears that both the oxidized and reduced form of riboflavin are associated with salicylic acid derivatives.

• Journal of Pharmaceutical Investigation
• /
• 제22권1호
• /
• pp.41-48
• /
• 1992

Six common tablet disintegrants (corn starch, Avicel PH102, calcium carboxymethylcellulose, Primojel, Kollidon CL and Ac-Di-Sol) were used at the concentration of 0, 2, 4 and 6% (w/w) in salicylamide tablets made with wet granulation method. Certain physical parameters of the disintegrants (moisture sorption, hydration capacity and bulk density) were determined to evaluate their relative efficiency. The disintegration time and dissolution rate of the tablets were correlated well with the ranks of initial rate of moisture sorption for each disintegrant as follows; Ac-Di-Sol, Kollidon CL, primojel, calcium CMC, corn starch and Avicel PH102. The initial rate of moisture sorption was important for the disintegration capacity as well as hydration capacity. The effect of storage at different temperatures and relative humidity upon the tablets containing various disintegrants was evaluated in terms of tablet hardness and disintegration time. Storage at high temperature reduced the hardness substantially and retarded the disintegration of the all tablets studied. Especially, the hardness of tablets containing Kollidon CL was significantly reduced. Although the tablet hardness was decreased and the disintegration time was increased under a moderate humid condition, both of them were decreased under the severely high humid condition of 80 or 90% RH, which was due to the breakrupture of tablet matrix bonds by the excessive uptake of moisture. Therefore, the stability caused by moisture sorption should be considered, when disintegrants having high moisture sorption such as Kollidon CL, Ac-Di-Sol and Primojel were employed in the tablets containing water-labile or hygroscopic drugs.

• 약학회지
• /
• 제28권2호
• /
• pp.101-127
• /
• 1984

The study of interaction between riboflavin derivatives and biologically active substances was reviewed. With combination of spectroscopic methods such as NMR, UV, Fluorescence and IR, informations about interaction mechanism including hydrogen bond formation, conformation of association complex, and association constant were obtained. 1. Riboflavin associated with adenine but not with other bases found in the nucleic acids. -CONHCO- group was included in the formation of hydrogen bond with adenine. 2. Riboflavin interacted with alcohol to make a 1 : 1 association complex through the 3N-imino and 2C-carbonyl group of the isoalloxazine ring and the hydroxyl group of the alcohols. 3. Riboflavin associated with salicylates to produce the cyclic hydrogen-bonded dimer. The strongest complex was formed with salicylic acid, a weaker one with aspirin, and an even weaker one with salicylamide. 4. Other bio-active substances, orotic acid and inhibitors such as phenol, trichloroacetic acid and indol also formed hydrogen bond with riboflavin. 5. Reduced riboflavin showed strong self-association to produce the cyclic hydrogen-bonded complex and it associated with adenine and with cytosine to form 1 : 3 complex.

• Archives of Pharmacal Research
• /
• 제24권3호
• /
• pp.171-179
• /
• 2001

The present investigation deals with the synthesis of some new salicylamidoacetyl sulfonamides 3a,b, salicylamido ethylacetate 4, salicylamido acetic acid hydrazide 5, which is considered as the key intermediate for the synthesis of several series of new compounds such as salicylamido pyrazol 6 and pyrazolone 1. N-imido-derivatives 9, 10, 11, thiadiazole 13, oxadiazole 14, 15, Schiffs bases 16a-f. Cyclocondensation of Schiffs bases with thioglycolic acid gave thiazolidinone 18a-c while with acetylchloride afforded azitidinones 19a-c and with acetic anhydride gave 1,4-benzoxazepine-3,5-dione. Some of the compounds were tested for their analgesic and antiinflammatory activities as well as ulcerogenic effects. Some derivatives were more effective than salicylamide and ulcerogenic activity was variably lowered .

• Toxicological Research
• /
• 제8권2호
• /
• pp.191-203
• /
• 1992

The immunosuppressive effects of safrole were studied in female BALB/c mouse. Mice were given 100,200and 400mg safrole/kg daily for 14days and evaluated on day 15. The day 4 immunogloblin-M antibody response to T-dependent antigen, sheep red blood cells (SRBC) was inhibited dose-dependently in all doses studied. In vitro antibody response to polyclonal antigen, lipopolysaccharide (LPS) by spleen cell suspensions from safrole-treated mice were also significantly inhibited. When safrole was treated for 14days to mice, and mitogen-induced proliferation of splenocytes were assayed on day 15, there were significant suppression of responses to B-cell mitogen, LPS and T-cell mitogen concanavalin A(Con A) at a dose of 400mg safrole/kg. Direct addition of safrole on the splenocyte culture also produced a dose dependent suppression on in vitro antibody response to LPS, and mitogen-induced lymphoproliferatin at doses of 100,200,400 and 800${\mu}M$ safrole. The role of metabolic activation in safrole-induced suppression of in vitro antibody response was studied using splenocyte-hepatocyte coculture system. The suppression of in vitro antibody respose to LPS by safrole was not altered when safrole were incubated in the splenocyte-hepatocyte system for 4hr as compared with direct addition of safrole in splenocytes culture. Neither the addition of salicylamide, sulfotransferase inhibitor, nor the addation of inorganic sulfate, sulfation cofactor to the splenocyte-hepatocyte coculture, altered the suppression of antibody response by safrole. These results suggest that the immunosuppression by safrole may not by produced by the reactive metabolites which are mediated in carcinogenesis of safrole.