NEW THERAPEUTIC AGENTS FOR GALLSTONE DISSOLUTION

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The primary treatment for gallstones is surgical removal. With a 1% mortality rate and substantial hospitalization costs, a search for less expensive and safer treatment for gallstone dissolution is warranted. It has been shown that gallstones consist primarily of cholesterol and their formation is a consequence of exceeding the solubility limits of cholesterol in the bile. As a result, it has been proposed that oral treatment with suitable bile acids may act as a gallstone dissolving agents, thereby eliminating the need for surgery. The goal of this project is to demonstrate that short chain analogs of head group modified phosphatidylcholines have superior solubilizing properties, compared with other potential cholesterol solubilizing agents relative to the amount and speed at which they can dissolve pre-existing cholesterol crystals. Should Phase I studies be successful, then Phase II studies would concentrate on the ability of oral intake of modified phosphatidylcholines to enter into the enterohepatic circulation in animal models. Phase III testing would consist of preliminary human studies.