Description

Initially, a clinical study was carried out for the first time to investigate the effect of Olivomed, a nutritional supplement containing Hydroxytyrosol, in patients with coronary artery disease. More specifically, a prospective, randomized, cross-over, double-blind, placebo-controlled, clinical trial was designed in which patients with chronic coronary syndrome were randomized into two groups and received either the dietary supplement Olivomed or placebo for one month. Cardiac and endothelial function, arterial stiffness and inflammation in the vessel wall were evaluated, as well as oxidative stress at baseline and after treatment.

In parallel with the implementation of the clinical study, olive components with beneficial properties such as hydroxytyrosol, oleuropein, oleanolic acid and oleocanthal were obtained on a large scale using green extraction and separation techniques. These molecules were isolated in pure form and in large quantities using modern techniques so that they were available for the in vivo experiments. Specifically, their cardioprotective effect was studied, using experimental murine model of metabolic syndrome. The olive components were administered orally daily for 6 weeks. Their potential effect in reducing blood glucose, circulating lipids or blood pressure, their effect on cardiac function (ultrasound examination) and their ability to limit the extent of myocardial injury after infarction were investigated. In order to determine the infarct size and further investigate the molecular mechanism of cardioprotection, mice were subjected to 30-min myocardial ischemia followed by 2-h reperfusion. Subsequently, an innovative approach was applied to determine the optimal combination of active ingredients. This approach combines in vitro studies, and more specifically the effect of isolated substances on the oxidative modification of LDL, with stoichiometric methods and prediction models (isobolograms). Therefore, 3 “smart mixtures” were designed as candidates for the development of a final new product.

These mixtures were retested in vivo, in the same experimental murine model of metabolic syndrome and their cardioprotective effect was examined as described above. A key point in the experimental study was the performance of the sub-acute toxicity study to document the safety profile. After verifying the effectiveness and safety of the final mixture, the coordinating company of the project, Unipharma, in close collaboration with Pharmagnose and the Division of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, proceeded with the development and production of a new food supplement, Olivomed-Smart, which contains the mixture of ingredients with the strongest beneficial actions in myocardial infarction and metabolic syndrome. After the development, implementation and validation of the control methods of the final product, Olivomed-Smart, was tested in a clinical study to investigate its effect in patients with coronary artery disease. The primary and secondary endpoints of the clinical study, as well as the implementation methodology were identical to the first clinical study that took place in the project. In this way, it became possible to compare the results of the two clinical studies in order to evaluate the effectiveness of the innovative preparation Olivomed-Smart compared to Olivomed in the prevention and treatment of coronary artery disease.