Based on the conducted pharmacological, clinical and pharmacoeconomic analysis of the detoxifying activity of the studied combination of taurine with sodium hypochlorite, the ways of optimization of infusion therapy in patients with acute pancreatitis are substantiated.
A single intravenous injection of both a solution of "Neoreodes" in the dose range from 1/10 to 2 CBV (ie, exceeding the recommended maximum single amount of the drug in 2 - 20 times) and 20-fold dose of comparison drugs did not cause death of rodents and did not affect the consumption of food and water, as well as the dynamics of body weight of experimental animals throughout the observation period.
It is shown that under the conditions of experimental chronic endotoxicosis caused by the introduction of carbon tetrachloride and bacterial lipopolysaccharide LPS, there was a significant increase in concentrations of MDA and DC by 102% (p ≤ 0.05) and 133% (p ≤ 0.05), respectively, indicating significant activation of lipoperoxidation processes. There was a significant decrease in the activity of SOD in liver tissue by 44% (p ≤ 0.05). In addition, the study of serum transaminases revealed a significant increase in the level of ALT and AST relative to the control group by 212% (p ≤ 0.05) and 147% (p ≤ 0.05), respectively. Such dynamics of changes of these indicators could serve as a marker of cytolysis of hepatocytes under the influence of damaging agents. Decreased SOD activity indicated a lack of antioxidant protection activity, which naturally leads to the large number of toxic catabolites accumulation in the blood and tissues that can cause immune system reactions.
Apparently, the difference between Neoreodez compared to the extemporal 0.06% sodium chloride and 0.09% taurine substance appears to be antagonistic to the growth of P. Aeruginosa test culture.
It was established that before the 10th and 15th days of the experiment, the intensity of the change in the surface area of the wound in the animals, which were applied "Neoreodez", became 38% and 65% as expected. Among the brews that were applied the extemporal NaClO solution, the area of the wound surface also decreased by 38% and 65% by 10th and 15th day, correspondingly. At the same time, in the control group of animals and in the group of rodents, which were tested for the difference in the taurine substance, the reparation processes were characterized by a decrease in the area of damage by 25% and 55% by 10th and 15th day compared to the initial background.
Evaluation of the effect of “Neoreodesis” intravenous administration on the blood coagulation system was performed on the basis of studying the basic coagulation tests (activated partial thromboplastin time and prothrombin time), as well as using a test to assess the state of vascular - platelet aggregation hemostasis – induced platelets aggregation .
It was found that under the influence of all studied activators (ADP 5 and 20 μm, collagen 2 mg / ml) there was a significant decrease in both the maximum degree and the rate of induced aggregation compared with the control group.
The next stage of our research was to evaluate the tolerability of a new detoxifying solution - a fixed combination of sodium hypochlorite and taurine in healthy volunteers, as well as to establish the effectiveness of acute pancreatitis treatment by determining the appropriate dosage regimen of the test drug, taking into account previously obtained in the experiment data on the presence of detoxifying, antimicrobial and wound-healing properties of the test sample.
The test sample does not cause side effects and phenomena, pathological changes in laboratory parameters of blood and urine, negative changes in hemodynamic parameters and ECG changes and objective examination data, which allowed to recommend it for stage II clinical trials.
The open, randomized comparative, parallel trial involved 96 patients with acute pancreatitis aged 18 to 65 years. The degree of endogenous intoxication was assessed by determining the molecules of the medium weight (MMW) by spectrometry in different modes - X = 254 nm and X = 280 nm. It is convincingly proved that the use of sodium hypochlorite with taurine infusion solution in the basic therapy significantly increases the effectiveness of treatment in patients with acute pancreatitis compared with the group of patients receiving basic therapy of acute pancreatitis only: the overall effectiveness of treatment with a new detoxifier was 91.67%, which is significantly higher than the corresponding figure in the control group - 60.4%.
We believe that the results of our experimental study and phase I and II clinical trials of sodium hypochlorite with taurine infusion solution allow us to recommend a new detoxifier for a comprehensive program to eliminate endotoxicosis in patients with acute pancreatitis.
