Methods and systems for modulating hormones and related methods, agents and compositions
Inventors
Goddard, III, William A. • MENNA, Mark • PANDOL, Stephen • Abrol, Ravinder
Assignees
California Institute of Technology • US Department of Veterans Affairs • University of California San Diego UCSD
Publication Number
US-9272051-B2
Publication Date
2016-03-01
Expiration Date
2031-06-17
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Abstract
Provided herein are bitter taste receptor ligands, related agents, combinations, compositions, methods and systems for modulating release of a metabolic hormone in vitro or in vivo from cells of the GI tract of an individual.
Core Innovation
The invention provides methods, systems, and compositions for modulating the release of metabolic hormones from cells of the gastrointestinal (GI) tract by administering ligands of GI bitter taste receptors. The modulation involves binding of one or more specific bitter taste receptor ligands to GI bitter taste receptors, resulting in alteration of the release of metabolic hormones such as GLP-1, PYY, and CCK, and controlling related biological processes. The invention also describes agents comprising bitter taste receptor ligands conjugated with complementary molecules to interfere with their systemic absorption and prolong their action in the GI tract.
The invention addresses the challenge of controlling hormone production and specifically modulating hormone release for treatment of various conditions in an individual. It provides new approaches to identify ligands capable of modulating hormone release by targeting bitter taste receptors in the GI tract, controlling their modulation, and using combinations of ligands or conjugates with complementary molecules to regulate the pharmacokinetics of the agents. Additionally, the invention includes methods to identify biological responses associated with bitter receptor activation and to screen candidate ligands for their ability to modulate metabolic hormone release.
Claims Coverage
The patent includes two independent claims directed to specific compositions combining 6-n-propylthiouracil with complementary molecules for modulating bitter taste receptor activation in the gut.
Composition comprising 6-n-propylthiouracil conjugated with polyethylene glycol
A composition comprising a combination of 6-n-propylthiouracil and polyethylene glycol, wherein the polyethylene glycol is conjugated to the 6-n-propylthiouracil, interferes with systemic absorption and release upon enteral administration, and results in prolonged activation of bitter taste receptors in the gut.
Composition comprising 6-n-propylthiouracil conjugated with cellulose
A composition comprising a combination of 6-n-propylthiouracil and cellulose, wherein the cellulose is conjugated to the 6-n-propylthiouracil, interferes with systemic absorption and release upon enteral administration, and results in prolonged activation of bitter taste receptors in the gut.
The claims cover compositions wherein 6-n-propylthiouracil is conjugated to specific complementary molecules like polyethylene glycol or cellulose to minimize systemic absorption and prolong activation of GI bitter taste receptors, thereby modulating metabolic hormone release.
Stated Advantages
Prolonged activation of bitter taste receptors in the gut by minimizing systemic absorption of the bitter taste receptor ligand.
Targeted modulation of metabolic hormone release for treatment or prevention of metabolic conditions.
Use of conjugates to improve pharmacokinetic properties such as sustained presence and reduced adverse effects.
Documented Applications
Medical applications including treatment and prevention of metabolic conditions such as obesity, diabetes, liver diseases, and cardiovascular diseases by modulating metabolic hormone release.
Biological analysis, food processing, taste/flavor modulation, nutrition, and nutraceutical applications involving modulation of GI and intestinal bitter taste receptors.
Diagnostics and clinical applications involving hormone modulation via GI bitter taste receptors.
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