Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects

Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come to age over the past few years. With regards to O3, its mechanisms of action in medicine have been clarified during the last two decades so that now a comprehensive framework for understanding and recommending ozone therapy in various pathologies is available. O3 used within the determined therapeutic window is absolutely safe and more effective than golden standard medications in numerous pathologies, like vascular diseases. However, ozone therapy is mostly in practitioners' hands and some recent developments for increasing cost effectiveness and speed of treatment are neither standardized, nor evaluated toxicologically. Hence, the aim of this article is to emphasize the need to objectively assess the pros and cons of oxygen/ozone as a medical gas mixture in the hope that ozone therapy will be accepted by orthodox medicine in the near future

Ozone acting on human blood yields a hormetic dose-response relationship

The aim of this paper is to analyze why ozone can be medically useful when it dissolves in blood or in other biological fluids. In reviewing a number of clinical studies performed in Peripheral Arterial Diseases (PAD) during the last decades, it has been possible to confirm the long-held view that the inverted U-shaped curve, typical of the hormesis concept, is suitable to represent the therapeutic activity exerted by the so-called ozonated autohemotherapy. The quantitative and qualitative aspects of human blood ozonation have been also critically reviewed in regard to the biological, therapeutic and safety of ozone. It is hoped that this gas, although toxic for the pulmonary system during prolonged inhalation, will be soon recognized as a useful agent in oxidative-stress related diseases, joining other medical gases recently thought to be of therapeutic importance. Finally, the elucidation of the mechanisms of action of ozone as well as the obtained results in PAD may encourage clinical scientists to evaluate ozone therapy in vascular diseases in comparison to the current therapies

A realistic evaluation of the action of ozone on whole human blood

We have clarified the role of the ozone concentration in relation to the resistance of human erythrocytes in whole human blood or in blood diluted either in saline or in distilled water. Spectrophotometric data related to haemoglobin were evaluated by exposing samples of fresh human blood directly to ozone doses (ratio 1:1 volume), within the therapeutic range (0.21–1.68 mM) and to one toxic dose (3.36 mM). Furthermore, the same determinations have been carried out after previous dilution of the same blood with either pure water or physiological saline (1 ml blood + 29ml diluent) followed by ozonation with the above reported ozone doses. Addition of either saline or water implies a dilution of plasma antioxidants and also total haemolysis after water dilution. Particularly the latter case represents a most unphysiological situation because the osmotic shock causes the solubilization of the erythrocytic content. While it is possible to demonstrate that after haemolysis there is an ozone-concentration dependent transformation of some oxyhaemoglobin to methaemoglobin, no such process occurs after ozonation of whole blood. The results of this study fully confirm our previous data that judicious ozone doses neither damage erythrocytes, nor induce oxidation of intracellular haemoglobin. We hope that our conclusions will definitively clarify the absence of toxicity of ozonetherapy

Commercial pregelatinized starches: ability to settle and rheological evaluation.

The ability to settle and the tribological properties of three samples of pregelatinized starch widely available commercially were investigated with reference to their technological implications. In particular, we evaluated the influence of storage conditions, storage time, moisture content, equipment, handling, and mechanical treatment on the apparent volume, poured density and tapped density, as well as on tests of flow parameters such as basic flowability energy. The results obtained highlight the fact that the technologically relevant behaviour of pregelatinized starches in terms of apparent volume and tribological properties may be influenced not only by relative humidity (RH%) conditions, but also by common pharmaceutical operating practices. In particular, previous mechanical treatment can lead to statistically different behaviour in tests of ability to settle according to pharmacopoeial specifications, depending on both RH% conditioning and the amount of powder, although the materials under investigation all conform to the respective monograph in the Pharmacopoeia. All these aspects are of special interest with regard to the various pharmaceutical formulations which include pregelatinized starch, both on an industrial scale and in small-scale production

Spectroscopic characterization of both aqueous and solid-state diacerhein/hydroxypropyl-β-cyclodextrin inclusion complexes

Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HPβCD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1 M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37 C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HPβCD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi-Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution. © 2014 Elsevier B.V. All rights reserved