Palatable compositions including sodium phenylbutyrate and uses thereof

Abstract

The present invention features palatable pharmaceutical compositions including sodium phenylbutyrate and methods for the treatment of inborn errors of metabolism (e.g., Maple Syrup Urine Disease or Urea Cycle Disorders), neurodegenerative disorders such as Parkinson's disease, spinal muscular atrophy, dystonia, or inclusion-body myositis with such compositions.

Description

BACKGROUND OF THE INVENTION[0001]Inborn errors of metabolism are a class of disorders arising from congenital disorders of metabolism. Many of the disorders are the result of defects of single genes that code for enzymes important for metabolism of certain substrates. The reduced activity of the enzymes results in accumulation of substrate to toxic levels which, in turn, leads to various symptoms depending on the substrate.[0002]Deregulation of branched chain amino acid catabolism leads to an inborn error of metabolism known as maple syrup urine disease (MSUD). MSUD, also referred to as Branched-Chain Keto Aciduria, is an autosomal recessive disorder, typically diagnosed within 4-7 days after birth, with an incidence of approximately 1 in 185,000 live births. MSUD is caused by mutations that result in a deficiency in the mitochondrial branched-chain ketoacid dehydrogenase complex (BCKDC), resulting in the accumulation of the BCAAs (leucine, valine, isoleucine) and their correspondin...

AI Technical Summary

Benefits of technology

This patent describes a drug that is used to treat inborn errors of metabolism. The drug is taken in high doses and needs to be mixed with a taste-mask coating to prevent it from being too strong in the mouth. The patent also describes a method of making the drug and using it to treat patients. The drug can be combined with other drugs and can help prevent infections and diseases associated with the metabolic disorders. The patent also mentions the use of a lubricant to prevent the ingredients from sticking together and the use of a seal coat to protect the ingredients from deterioration.

Problems solved by technology

The reduced activity of the enzymes results in accumulation of substrate to toxic levels which, in turn, leads to various symptoms depending on the substrate.

If left untreated MSUD patients develop high BCAA levels and suffer from chronic and acute neurological damage, including low IQ, mental impairment (poor cognitive function), social impairment (poor executive function), and metabolic decompensation (seizures and coma), central respiratory failure, and death may follow.

In UCD, a mutation causes a deficiency in an enzyme of the urea acid cycle (for example N-acetylglutamate synthetase, carbamoyl phosphate synthetase I, ornithine transcarbamylase, argininosuccinic acid sythetase, argininosuccinic acid lyase, or arginase) and can result in life-threatening neurological complications.

All forms of SMA are caused by homozygous loss of the functional survival motor neuron (SMN1) gene resulting in insufficient levels of the SMN protein.

The commercially available formulations of immediate release sodium phenylbutyrate (e.g., BUPHENYL®) are unpalatable due to taste that is highly unpleasant.

Noncompliance due to the poor taste can lead to insufficient dosing and suboptimal outcomes.

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