Ceskoslovenska farmacie最新文献

Resistant strains of Escherichia coli were obtained by stepwise cultivation in subinhibitory concentrations of two antimicrobially active amine oxides. Changes in the chemical composition of the outer membrane of the resistant strains were accompanied also by different antigenic reactions. New precipitation lines were revealed by double immunodiffusion and immuno-electrophoretic methods. The results of immunochemical analysis confirm the findings that the resistance to amphiphilic compounds is associated with the outer membrane which limits the access of antimicrobially active molecules to their sites of action in the cytoplasmic membrane.

The preceding study of the effect of the branching of the connecting chain by the metoxymethyl-, ethoxymethyl- and propoxymethyl group on the alpha carbon on local anaesthetic activity was a stimulus for the preparation of 16 drugs of the group of 1-ethoxyethoxymethyl-2-(1-pyrrolidinyl-), 2-piperidino- and 2-(1-perhydroazepinyl) ethyl esters of o-, m- and p-alkoxyphenylcarbamic acids. The discontinuation of the substituent on the alpha carbon of the connecting chain by another oxygen atom (introduction of an ethoxyethoxymethyl group) has a positive effect on surface and infiltration anaesthesia. Of the prepared agents, 2-piperidino- and 2-(1-perhydroazepinyl-) derivatives with a hexyl or heptyloxy group in the o-position of the benzene ring were most effective; they exceeded the standards cocaine and procaine more than one hundred times. p-Derivatives were least effective; in some cases their indices of effectiveness did not achieve the effectiveness of the standards in both surface and infiltration anaesthesia under study. Acute toxicity of all drugs lies within the range of the toxicities of the standards.

The activity of peptidases (trypsin from bovine pancreas and trypsin-like enzymes from the liver rat homogenate) was influenced by five preparation of Kampo medicine, TJ-9 (Sho-Saiko-To), TJ-15 (Oren-Gedoku-To), TJ-23 (Toki-Shakuyaku-San), TJ-96 (Saiboku-To), and TJ-114 (Sairei-To) and studied in relation to their effect on the uptake of free oxygen radicals demonstrated earlier. On the basis of increased activity of trypsin and trypsin-like enzymes and the previously found capability of uptaking free oxygen radicals, the mechanism of action of the Kampo preparations may be assumed to be connected not only with a direct support of enzymes of digestion and increased activity of peptidases, capable of eliminating oxidatively damaged proteins, but with an antioxidative effect as well, which prevents increased cumulation of oxidatively damaged macromolecules and the action of superoxide radicals developed earlier by the well-known and trypsin-stimulated conversion of xanthinedehydrogenase to xanthinoxidase.

TJ-15 (Oren-Gedoku-To) inhibited enzymatically (NADPH or CumOOH) and non-enzymatically (Fe-askorbate) induced lipid peroxidation in the rat liver microsomes as assessed by the TBA-reactive product accumulation. TJ-23 (Toki-Shakuyaku-San) had little effect on either system. The protective effect of TJ-15 against lipid peroxidation could not be fully accounted for by its action on microsomal electron transfer, as evaluated by studying the kinetics of reduction of cytochrome C. In a free solution TJ-15 and TJ-23 effectively scavenged OH., radicals, as indicated by the inhibition of ethylene production from KMBA, and O2-. anion radicals, as assessed by the inhibitory effect on the rate of NBT reduction. The present results suggest that TJ-15, yet not TJ-23, is capable to reach hydrophobic intra-membrane sites at concentrations at which it is an effective antioxidant. Thus TJ-15 may be a potentially useful protective agent against free radical-mediated damage.

Within the framework of the research of potential local anaesthetics, five compounds from the group of (+/-)-trans-[2-(piperidino-methyl)cyclopentyl]alkyl, alkoxy and chloroalkyl esters of phenylcarbamic acid were prepared. The final compounds were obtained by addition of (+/-)-trans-2-(piperidinomethyl)cyclopentanol to the corresponding substituted phenylisocyanates. They were isolated in the form of salts with hydrochloric acid. Their structure was confirmed on the basis of interpretation of the results of UV and IR spectra. A pharmacological evaluation revealed that the final compounds were more effective than the employed standards cocaine and procaine, but they did not achieve the expected effect in comparison with the pattern compound pentacaine. The index of local-anaesthetic efficacy ranges from 1 to 8 in surface anaesthesia and 1 to 12 in infiltration anaesthesia. It is substantially lower even in comparison with analogical basic esters of alkoxyphenylcarbamic acid.

Experiments carried out on male mice (ICR) demonstrated a protective effect of premedication with the preparation Sho-Saiko-To (TJ 9, Tsumura and Comp.) against the hepatotoxic effects of CCl4 and T1-acetate, which were manifested by increased peroxidation of lipids and increased depletion of reduced glutathion in liver homogenates.