Hydrolysis kinetics and QSAR investigation of soft antimicrobial agents.

Quaternary ammonium surfactants, such as benzalkonium chloride and cetylpyridinium chloride, are commonly used as antibacterial agents for disinfectants and for general environmental sanitation, as well as in surfactants, penetration enhancers and preservatives in pharmaceutical and cosmetic formulations. However, these agents are known to cause various side-effects and toxic reactions that are believed to be associated with their chemical stability. Soft analogues of the long-chain quaternary ammonium compounds were synthesized according to the soft drug approach and their physicochemical properties investigated, such as their hydrolytic rate constant, surface activity and lipophilicity. Structure-activity studies showed that the antimicrobial activity of the compounds was strongly influenced by their lipophilicity and chemical stability, the activity increasing with increasing lipophilicity and stability. However, in soft drug design structure-activity relationships are combined with structure-inactivation relationships during the lead optimization. The safety index (SI) of compounds was defined as the hydrolytic rate constant divided by the minimum inhibitory concentration. The SI of the soft antibacterial agents was found to increase with increasing lipophilicity but optimum SI was obtained when their hydrolytic t1/2, at pH 6 and 60 degrees C, was about 11 h. Optimization of the soft antibacterial agents through SI optimization resulted in potent but chemically unstable quaternary ammonium antibacterial agents.

Unfolding and refolding of bovine serum albumin induced by cetylpyridinium bromide.

The interaction of bovine serum albumin (BSA) with cationic surfactant cetylpyridinium bromide (CPB) in aqueous solution (pH 7.00) was studied quantitatively with ultraviolet (UV)-visible, far-UV, and near-UV circular dichroism, fluorescence, small angle x-ray scattering, and nuclear magnetic resonance measurement. It was found that CPB at low and high concentrations could induce the unfolding and refolding of BSA, respectively. We suggest that in the unfolding process, there existed BSA-CPB complex with the "necklace and bead" structure in which the unfolded BSA wrapped around CPB micelles, and that the hydrophobic interaction between the complexes led to the formation of large aggregates. The aromatic headgroup of CPB interacted with the tryptophan residues of BSA, resulting in the aromatic ring stacking between BSA and CPB. During the refolding process, the BSA molecule was penetrated into the rod micelle of CPB and the hydrophobic moiety of the BSA molecule was exposed outside while its hydrophilic part was hidden inside, thereby disrupting the aromatic ring stacking.

Cetylpyridinium tetrachlorozincate as standard for tenside titration. Analytical methods with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in respect to environmental and economical concern, part 19.

The determination of the cationic active disinfectants benzalkonium chloride, benzethonium chloride, cetrimide, and cetylpyridinium chloride according to PH. EUR. 2002 resp. supplement 4.3/2003 can be improved using the DBH-method. By application of column extraction the iodide determination can be performed in the organic layer by visual indication. However, titration in aqueous solution with sodium dodecyl sulphate as titrant and methyl orange resp. bromophenol blue as indicator can be performed more simple. Cetylpyridinium tetrachlorozincate is recommended as a standard for tenside titration.

A double-blind, vehicle-controlled study of the safety and efficacy of Fungoid Tincture in patients with distal subungual onychomycosis of the toes.

Onychomycosis is one of the most common causes of nail disease and one of the hardest to treat among fungal infections. A double-blind, vehicle-controlled study has been conducted to evaluate the safety and efficacy of Fungoid Tincture (Pedinol Pharmacal, Inc), for the treatment of fungal infection of the toenails. Ten patients with distal subungual onychomycosis were treated for twelve months with topical Fungoid Tincture. Another ten patients with the same ailment were treated with the vehicle alone. Once a month, clinical and global evaluation of the target nail was done, in addition to trimming and debridement of the nails. After twelve months of treatment, 90 percent of patients applying Fungoid Tincture showed negative results on culture. There were minimal adverse effects.

Open-label study of the safety and efficacy of Fungoid tincture in patients with distal subungual onychomycosis of the toes.

Onychomycosis is the most frequent cause of nail diseases. An open-label study has been conducted to evaluate the safety and efficacy of Fungoid Tincture, a topical antifungal agent approved by the Food and Drug Administration for the treatment of onychomycosis of the toes. Ten patients with culture-proven distal subungual onychomycosis were treated twice daily for twelve months with topical Fungoid Tincture. Another ten patients with the same condition were treated with the vehicle alone. At monthly intervals, the target nail was trimmed, the nail bed debrided, and global clinical assessment recorded. After twelve months of therapy, all patients applying Fungoid Tincture showed negative findings on fungal culture. The vehicle alone benefitted several patients, and may have antifungal activity. Adverse effects were minimal, with mild peeling occurring in seven patients and erythema noted in one.

An evaluation of 1-hexadecylpyridinium chloride as a decontaminant in the primary isolation of Mycobacterium bovis from bovine lesions.

For the primary isolation of Mycobacterium bovis from bovine lesions, 1-hexadecylpyridinium chloride (HPC) at a concentration of 0.75% was as effective as 2% NaOH in controlling the growth of contamination. The advantages of using HPC over NaOH are that it is a rapid one-step procedure not requiring neutralisation with acid, it is less toxic to M. bovis thus increasing isolation rates, and it promotes the earlier appearance of colonies.

What is in the surgeon's glove?

Three aspects of surgical hand hygiene have been studied: the attitude of the surgeon, the microbiology of glove changing during an operation, and the use of antiseptic-coated gloves together with different handwash routines. The survey revealed that the predominant factor in choice of agent for surgical hand hygiene was skin tolerance. The microbiological studies showed that 'closed' glove changing was to be preferred to 'open' changing, and that antiseptic-coated gloves further suppressed the skin flora, even after prolonged operations, compared to standard gloves.

[Modification of the immune response by using an antigen bound to synthetic polyelectrolytes]. / Modifikatsiia immunnogo otveta pri pomoshchi antigena, sviazannogo s neprirodnymi poliélektrolitami.

The immunogenic properties of the soluble complexes of bovine serum albumin (BSA) and synthetic polyelectrolytes were studied. The polyelectrolytes used in these complexes were 4-vinyl-N-ethylpyridinium bromide and 4-vinyl-N-cetylpyridinium bromide (complex I), 4-vinylpyridine and 4-vinyl-N-acetylpyridinium bromide (complex II). C57BL mice were immunized with different doses of BSA, complexes I and II introduced intraperitoneally in a single injection, and the number of plaque-forming cells (PFC) in the spleen was determined by modified Jerne's test with the use of BSA-covered sheep red blood cells. The above complexes were shown to stimulate the production of PFC against BSA 50-100 times more intensively than pure BSA. The mixtures of BSA with the above-mentioned polyelectrolytes stimulated PFC production to a considerably lesser extent. Thus, the polymeric part of these conjugates was not an antigen, but served as a carrier inducing pronounced immune response to the antigenic (protein) part of the complex.¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿¿