Orally available Sustained-Release Phenylbutyrate for Hyperammonemia

Potential application for Hepatic Encephalopathy and Urea Cycle Disorder

Advantages

– Improves efficacy of phenylbutyrate (PBA)
– Reduces administration frequency of PBA from 6 to 1 time per day
– Potential application for Hepatic encephalopathy and Urea cycle disorder

Description

 Hyperammonemia is caused by urea cycle disorder (UCD) or liver diseases such as liver cirrhosis. Phenylbutyrate (PBA) sodium, used for UCD, has an effect by facilitating the alternative ammonia detoxification route, but the effect is not high enough and three to six times per day administration is required due to its short half-time.
 We have developed a nano micelle formulation of phenylbutyrate by synthesizing block polymer composed of polyethylene glycol and vinyl phenylbutyrate, which self-assembles in water: Phenylbutyrate Nanoparticle (Ph-BNP). Orally administered Ph-BNP accumulates in the intestinal mucosa and gradually releases PBA over more than 24 hours.
Ph-BNP could overcome the problem of PBA and has potential to be a novel treatment of hepatic encephalopathy, a common manifestation of hyperammonemia, as well as UCD.

Continuous removal of ammonia through gradual release of Phenylbutyrate

Data

Effect on Hyperammonemia

Orally Administrated Ph-BNP effect was evaluated by hyperammonemia model mice induced from acetaminophen IP injection.

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Product No. MR-03169b

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