Composition for Treatment of Acute and Chronic Hepatic Encephalopathy

 

Definition: Hepatic encephalopathy (HE)-brain dysfunction determined by liver insufficiency to filter out gut ammonia and related toxins.

The aim: Development of combined preparations, which may be used as pharmaceutical compositions or as dietary supplements, which enable to prevent, delay or relief the neurocognitive and metabolic disorders, related to HE, liver, brain, vascular system, etc. dysfunction.

Current state: Most common therapeutic options are directed towards the treatment of precipitating factors and reduction of circulating ammonia («ammonia lowering strategies»-ALS), rather than on correction of the deterioration in the brain, liver, vascular system, etc. or on supportive therapy. ALS are used over last 50 years and are based on trapping of ammonia (L-ornitine-L-aspartate) or of ammonia and adaptively accumulated L- glutamine (L-ornitine-phenylacetate). More than 55 years ago W. McDermott, evaluating the efficacy of existing treatment options, based on amino acids therapy, wrote: it should not be expected that this will prove to be a universal panacea not should be expected than any one administered substance could effectively reverse all the derangements...

New offered approaches in the therapy of HE so cold «counteracting or neuroprotective strategies» are based on application of the inhibitors or antagonists of multiple proteins, attacked by ammonia or other toxins. Systemic application of them might have side effects.

Results: The etiology of HE is multifactorial and very complex and to address this issue the multi target therapy should be developed. Our strategy is focused on the development of group of medical preparations, representing complex formulations of compounds, having multiple functions and combined synergistic action on different targets, which are affected in the process of HE development. Based on animal study were run out preliminary treatment with different dosage of 45 patients (1 week treatment and 1 month treatment periods and 1 month follow up period), which have liver cirrhosis of viral etiology and hepatic encephalopathy. The study was performed on the basis of informed consent. We have Russian patent, PCT application and the License for the production of dietary supplements.

Conclusions: No adverse events were observed in both study groups. The results of this trial show that oral administration of claimed composition is safe, well tolerated and effective. It resulted in significant decrease in ammonia concentration with concomitant rise in CFF-test values and reduction of AAT activity and do not have rebound effect (the rise in ammonia concentration and fall of CFF values) after cessation of patients treatment, due to the fact that therapeutic effect is preserved during one month post treatment period.