Benorilate (Benoral)

Descriptors for some compounds with pharmacological activity; calculation of properties

Abraham model solute descriptors have been determined for nisoldipine, nizatidine, loratadine, zonisamide, oxaprozin, rebamipide, domperidone, temozolomide, 'florfenicol', florfenicol A, dapsone, chrysin, benorilate, β-lapachone, and Ipriflavone based on published partition coefficients, molar solubilities and gas chromatographic retention indices. The calculated solute descriptors, combined with our previously published Abraham model correlations, are used to predict several important physicochemical and biological properties, such as air-water, air-blood, air-lung, air-fat, air-skin, water-lipid, water-membrane and water-skin partition coefficients, as well as permeation from water through skin.

[Long-term toxicity of benorylate]

A long term study was carried out to determine the possible toxic effects of therapeutic doses of a suspension of benorilate on bone marrow, liver and kidneys in 33 patients with rheumatoid arthritis. 14 were male and 19 femal patients. 11 of the male and 14 of the female patients presented a positive rheumatoid factor. The duration of the treatment was first limited to 6 months. In 20 of the 33 patients duration of treatment was extended to 7 and 91/2 months. Three patients interrupted treatment after respectively 2, 3 and 5 months. Benorilate was given in a daily dosage varying from 6-8-12 g (as a suspension containing 40% benorilate). The following parameters were used to determine the effect of the drug on bone marrow: Hemoglobin, erythrocyte count, leucocyte count, thrombocyte count. Tests were done at regular intervals to determine a possible toxic effect on the kidney: urea nitrogen, uric acid, creatinine and urineanalysis were performed at regular intervals. To determine any possible hepatic toxicity, SGOT, SGPT, alkaline phosphatase and prothrombin time were done at regular intervals. On the basis of the laboratory results, no toxicity could be demonstrated in bone marrow, liver and kidneys when benorilate was given in therapeutic doses for the treatment of rheumatoid arthritis. Rare temporary abnormal laboratory values are not statistically significant and can be considered part of systemic involvement secondary to rheumatoid arthritis. The combination of the two active substances of benorilate decreases to a minimum on the one hand the above mentioned side effects and on the other potentiates the therapeutic and especially the analgetic effect. After resorption, the preparation is hydrolized in the plasma to acetylic salicylic acid and paracetamol. The hydrolysis takes place in the gastrointestinal tract which probably explains why the drug is so well tolerated.

Determination of benorilate in pharmaceutical formulations and its metabolite in urine at carbon paste electrode modified by silver nanoparticles

Benorilate was determined by the differential pulse voltammetry (DPV) using a carbon paste electrode modified by silver nanoparticles in 1.25x10(-3)moll(-1) KH(2)PO(4) and Na(2)HPO(4) buffer solution (pH=6.88, 25 degrees C) .The anodic peak potential was +0.970V (versus SCE). A good linear relationship was realized between the anodic peak currents and benorilate concentrations in the range of 1.0x10(-7) to 2.5x10(-4)moll(-1) with the detection limit of 1.0x10(-8)moll(-1). The recovery was 95.2-103.6% with the relative standard deviation of 3.6% (n=9). The pharmaceutical preparations, benorilate tablets samples and its metabolite (salicylic acid) in urine were determined with the desirable results.

"In vivo" effects of acetylsalicylic acid and two ether derived compounds on primary immune response and lymphoblastic transformation

A comparison was performed of acetylsalicylic acid and two ether derivatives (Benorilate and Eterilate) and indomethacin in order to ascertain the in vivo effects on the lymphoblastic transformation and the primary immune response in mice. The humoral response in Benorilate-and Eterilate-treated mice was 40-50% lower than that of the controls, whereas in acetylsalicylic acid-treated mice the response was only 25% inhibited. The number of immunoglobulin synthesizing cells was neither reduced by acetylsalicylic acid nor by its derivatives, although indomethacin treatments (used for comparative purposes) inhibited by 40% the number of direct plaque-forming cells on the days tested. Mitogen-induced proliferation of spleen lymphocytes was also inhibited in the treated mice; these inhibitions were negligible in the case of cells from acetylsalicylic acid-treated mice activated by concanavalin A and slight in cells from Benorilate-treated mice activated by bacterial lipopolysaccharide. When lymphocytes from drug-treated animals were further cultured in the presence of the same drug, a variable inhibition of mitogen-induced proliferation was observed. These different in vivo effects of acetylsalicylic acid and the two ether derivatives and indomethacin may be due to a distinct action on diverse lymphocyte subpopulations altering their cellular collaborative interactions or modifying the prostaglandin availability.

[Rapid identification 15 effective components of anti common cold medicine with MRM by LC-MS/MS]

This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.