Formulations of deoxycholic for therapy: a patent review (2011 – 2014)

Abstract

Introduction: Deoxycholic acid (DOCA) is involved in many physiological functions and has been used in various fields of pharmaceutical formulations as a natural active solubilizing and permeation-enhancing agent. Although DOCA has been suggested to be a promoter of colon cancer, it has also been used extensively as a starting material to obtain new derivatives for potential therapeutic applications.

Area covered: In this review, we focus on patents and research reports from 2011 to 2014 related to pharmaceutical formulations and therapeutic applications using DOCA and its derivatives as surfactants or absorption enhancers, drug delivery carriers, and anti-cancer agents.

Expert opinion: In recent few years, DOCA and its derivatives have been used mostly as pharmaceutical excipients for solubilizing lipophilic compounds to improve their bioavailability. Other studies have expanded its applications to include enhanced drug permeability and have designed more effective drug carriers by conjugation with polymeric materials. Recently, a synthetic DOCA injection, ATX-101, has shown long-term efficacy in the non-surgical treatment of unwanted submental fat and acceptable tolerability in humans. Thus, it may be used for reducing specific localized fat accumulations. Additionally, DOCA has been a starting material for anti-cancer drugs, and some derivatives showed strong inhibitory activities against several carcinoma cells.

Keywords:

• absorption enhancer
• anti-cancer
• bile acid
• deoxycholic acid
• lipolysis
• solubilizer

Article highlights

• Deoxycholic acid (DOCA) is a secondary bile acid (BA), which are metabolic byproducts of intestinal bacteria.

• An injection formulation of pure synthetic DOCA, ATX-101, has shown long-term efficacy in reducing subcutaneous fat deposits and tolerability in humans.

• Various DOCA derivatives have been synthesized and show inhibitory activity against carcinoma cells via inhibition of tumor invasion and proliferation, as well as promotion of apoptosis.

• DOCA and its derivatives can be used as solubilizing agents and/or absorption enhancers for oral, nasal, ophthalmic, transdermal, and parenteral drug delivery formulations.

• Nano-/micro-particulate vehicles using deoxycholate (DC) and its derivatives have been investigated extensively to increase the delivery efficiency of loaded drugs to the site of action.

• Chemical or physical conjugation of drugs with BA derivatives has been used to improve bioavailability.

This box summarizes key points contained in the article.

Declaration of interest

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, & Future Planning (NRF-2014R1A1A1003122), and Basic Research Program through the NRF, funded by the Ministry of Education (NRF-2014R1A1A2057483). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.