DARU, Journal of Pharmaceutical Sciences
Volume:11 Issue: 2, Summer 2003

Abstract: The partition coefficients (Kpart, in octanol/water system) of a range of bidentate ligands containing the 3-hydroxypyridin-4-one moiety were determined using shake flask and automated continuous flow methods (filter probe method)). The shake flask method was used for extremely hydrophilic or hydrophobic compounds with a Kpart values greater than 100 and less than 0.01. For other ligands which possess moderate lipophilicity (Kpart values between 0.01-100) the filter probe method was used. Also the partition coefficient of four ligands with moderate lipophilicity was determined by shake flask method in order to check comparability of these two methods. While the shake flask method was able to determine either extremely hydrophilic or hydrophobic compounds efficiently, the filter probe method was unable to measure such Kpart values. Although, determination of the Kpart values of all compounds is possible with the classical shake-flask method, the procedure is time consuming. In contrast, the filter probe method offers many advantages over the traditional shake-flask method in terms of speed, efficiency of separation and degree of automation. The shake-flask method is the method of choice for determination of partition coefficients of extremely hydrophilic and hydrophobic ligands.

Abstract: Viral safety of human plasma products plays a key role in their safe uses. Solvent- detergent (SD) virus-inactivation method has gained widespread popularity in the manufacture of biological products. This treatment which inactivates lipid-enveloped viruses effectively consists of incubation of a plasma protein solution in the presence of a non-volatile organic solvent and a detergent. In this study, IgM-enriched immunoglobulin was incubated at 24 °C for 6 h under slow stirring in the presence of tri(n-butyl) phosphate (0.3% w/w) as solvent and tween 80 (1% w/w) as detergent. After completion of the inactivation process and removal of the solvent-detergent, the ability of SD-treatment to remove Infectious Bovine Rhinotracheitis (IBR) virus (a lipid-enveloped virus) and Foot-and-Mouth Disease virus (a non-enveloped virus) were evaluated by "virus spiking studies" using a scaled down process. Reduction factor of 4 log was obtained for the SD-treatment of IgM-enriched immunoglobulin spiked with IBR virus. No virus inactivation was observed in the SD-treated IgM-enriched immunoglobulin, spiked with Foot-and-Mouth Disease virus. It was concluded that treatment of IgM-enriched immunoglobulin with TNBP-TWEEN 80 may be considered as an efficient lipid-enveloped virus inactivation step in the manufacture of this product.

Abstract: Tannic acid (TA) is naturally occurring polyphenols present in fruits and vegetables. In this study, inhibition of the carcinogenic potential of croton oil in normal and iron overloaded mice skin by TA is reported. Albino Swiss mice were given iron-dextran for two weeks and were pretreated with a single topical application of tannic acid. After one hour tumors were initiated by a single dose of 7,12- dimethylbenz(a)anthracene (DMBA) the promoting agent croton oil was applied twice a week for 30 weeks. The appearance, number and percent tumor incidences were recorded. When compared to control groups, the pretreated groups showed a significant high inhibition of tumors incidences. Biochemical studies in mice skin tissues were based on the measurement of lipid peroxidation (LPO). TA diminished cutaneous LPO level in mice skin as compared to the untreated groups. This study showed that TA inhibits the augmentation potentials of croton oil and iron dextran significantly. A depletion in LPO levels in TA pretreated groups indicates that excessive generated oxidants in the mice skin tissues may be quenched by TA because of chelation of redox active iron and its faster elimination from the body. It is supposed that inhibition of iron mediated oxidative stress by TA may be responsible for diminishment of cutaneous tumorigenesis.

Abstract: Sucralfate enema has been proposed and investigated in treatment of ulcerative proctitis, but its efficacy is still a matter of debate. Hydrocortisone enema is still an established drug in treatment of ulcerative proctitis. This study was designed to compare the effect of sucralfate enema with hydrocortisone enema. Patients with active sigmoidoscopic and histologic features of ulcerative proctitis were included. All patients had clinical manifestations of proctitis for at least four weeks prior to the study and had negative parasitic stool culture. The total of 25 patients entered the study. They were randomly divided in two groups; group I (n =14) and group II (n = 11) who received sucralfate and hydrocortisone enemas respectively for 4 weeks. Both groups had a significant improvement in clinical features, histologic activity and sigmoidoscopic evaluation in comparison with the baseline. Furthermore there was no significant differences between the two groups concerning mean changes of clinical, sigmoidoscopic, and histologic grading, after treatment. Considering the low cost and minimal adverse effects of sucralfate, and almost equal efficacy in comparison with hydrocortisone enema, its usage can be recommended.

Abstract: Due to the good anticonvulsant activity of various 1,2,4-triazoles, several new N4-substituted triazolylthiazoles were prepared by the general method for 1,2,4-triazole ring closure. Anticonvulsant activity of compounds was measured against pentylenetetrazole-induced seizures in mice by intraperitoneal injections of different doses of the test compounds. Pretreatment of animals with flumazenil (10 mg/kg, i.p.) as a benzodiazepine receptors antagonist did not have any significant effect on anticonvulsant activity of the test compounds. These results demonstrate that the anticonvulsant activity of N4-substituted triazolylthiazole agents is not probably mediated by direct interaction with benzodiazepine receptor complex.

Abstract: Hydrodistillation of aerial parts of Cymbopogon olivieri (Boiss.) Bar (Andropogonae) yielded 1.7% v/w of the essential oil. By GC and GC/MS twenty-two components, representing 94.80% of the total oil composition were identified. The major constituents were Δ-3 carene (22.46%), piperitone (44.90%) and α-eudesmol (13.33%). The essential oil of Cymbopogon olivieri (Boiss.) Bar showed interesting activity against larvaes of Anophel stephensi (LD50=321. 902 p.p.m.).