The use of 4-Hexylresorcinol as antibiotic adjuvant.

Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR.

[Oral cavity microbiocenosis assessment on the basis of bacterial endotoxin and plasmalogens in a saliva by method GAS-liquid chromatography-mass spectrometry.]

The concentration of plasmalogen bacterial and endotoxin levels in the saliva of patients with different severity of periodontal disease, injury prosthetic bed and with various degrees of the oral cavity microbiocenosis violations was studied. Determination of the presence of the pathological process was carried out clinically, according to the condition of periodontal tissues. The degree of microbiological disorders was assessed by the quantitative ratio of the types of microorganisms isolated from the smear taken from the gingival groove. It was found that the concentration of plasmalogen for normal microbiocenosis is not less than 0.7 µg/g. For the intermediate type of microbiocenosis, the concentration of 1.82 µg/g was determined; for dysbiosis - 5.64 µg/g, and for the expressed violation of the microbial composition accompanied by inflammatory processes - 6.54 µg/g. An increase in the concentration of bacterial endotoxin (be) more than 6.25 nanomole/g indicates the pronounced inflammatory process, regardless of the determined intensity of contamination of opportunistic gram-negative microflora.

[Rapid analysis of suppositories by quantitative 1H NMR spectroscopy].

Rapid analysis of suppositories with ibuprofen and arbidol by quantitative 1H NMR spectroscopy was performed. Optimal conditions for the analysis were developed. The results are useful for design of rapid methods for quality control of suppositories with different components

[Investigation of structural characteristics of initial substances of ibuprofen and micronization impact].

Structural characteristics of ibuprofen substances manufactured by different firms and the impact of micronization on them were compared. The study showed that the use of X-ray diffraction methods was necessary for certification of medicinals (crystalline) since only such methods provided information on the substance crystal structure, the molecular state and polymorphous forms.

[Scientific approaches to development of medicinal formulation based on biotechnological substance].

The study demonstrated possible design of a medicinal formulation in the form of suppositories comprising human recombinant interferon-alpha2 and dry aloe extract. The approaches to the development of the suppositories were technology-derived. No interaction between the active and auxiliary components was proved by solid state 1H-NMR spectroscopy. The specific activity of the drug was investigated.

[Preclinical investigation and standardization of metronidazole soft dosage forms].

Comparative acute and subacute toxicity of Dentamet gel and Metrovagin suppositories manufactured by ZAO Altaivitaminy was studied with using analogous drugs, i. e. Metrogil Denta, a gel for the gingivae, manufactured by Unique Pharmaceutical Laboratories (India), and Flagil manufactured by Haupt Farma Livron (France) as the reference drugs. It was shown that the drugs induced no changes in the exterior, hair state, body weight and mobility of the experimental animals vs. the control. The pharmacokinetic study of Metrovagin vaginal suppositories vs. the registered analogous drug Flagil showed that Metrovagin was bioequivalent to Flagil. The relative bioavailability of the new drug vs. the control was 103.13%.

[Determination of biological activity of hydrogel preparations based on ketoconazole and clotrimazole]. / Opredelenie biologicheskoi aktivnosti gidrogelevykh preparatov na osnove ketokonazola i klotrimazola.

Biological activity of original hydrogel preparations based on ketoconazole and clotrimazole was estimated biologically with the 3-dose variant of the agar-diffusion method. The optimal concentrations of the active substances in the hydrogels were the following: 2% of ketoconazole and 1% for clotrimazole.