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-8796233-B2
Publication Date
2014-08-05
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 relates to methods, systems, and compositions for modulating the release of metabolic hormones from cells of the gastrointestinal (GI) tract by targeting bitter taste receptors located therein. The inventive agents include bitter taste receptor ligands such as 6-n-propylthiouracil (PTU), phenylthiocarbamide (PTC), denatonium benzoate, and various derivatives thereof, which bind to GI bitter taste receptors and modulate the release of metabolic hormones like glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and cholecystokinin (CCK). The methods involve administering such ligands, alone or in combination and potentially conjugated to complementary molecules, into the GI tract to effect modulation of hormone release linked to related biological processes and metabolic conditions.
The problem addressed is the difficulty in effectively controlling hormone production, particularly the modulation of hormone release for treatment of various metabolic conditions. Existing approaches lack means to selectively modulate metabolic hormone secretion in a controlled manner. The present disclosure provides specific bitter taste receptor ligands and related agents capable of binding GI bitter taste receptors to achieve modulation of hormone release, thereby offering new strategies for treating metabolic diseases and associated conditions.
Claims Coverage
The patent contains multiple independent claims covering methods of modulating metabolic hormone release via GI bitter taste receptor ligands, agents conjugated with complementary molecules, and methods of activating bitter taste receptors.
Modulating metabolic hormone release using GI bitter taste receptor ligands conjugated with complementary molecules
Administering to an individual one or more GI bitter taste receptor ligands selected from a specified group conjugated with complementary molecules configured to interfere with systemic absorption, in an effective amount to bind GI bitter taste receptors and modulate release of hormones GLP-1, PYY, and/or CCK, via enteral administration.
Administering bitter tastant ligands conjugated with complementary molecules for receptor activation
Administering effective amounts of bitter tastant ligands conjugated to complementary molecules that reduce systemic absorption to activate target bitter taste receptors by enteral administration.
Formulating compositions to minimize systemic absorption and target GI bitter taste receptors
Formulating compositions comprising GI bitter taste receptor ligands to minimize systemic absorption across the GI epithelium and/or deliver ligands directly to specific intestinal cells (e.g., L-cells or I-cells) to achieve localized hormone modulation.
Use of specific bitter taste receptor ligands to increase metabolic hormone release
Using selected bitter receptor ligands including denatonium benzoate or derivatives to selectively increase release of specific metabolic hormones such as CCK, and using other ligands including PTU and PTC to increase GLP-1 and PYY release.
Treatment of metabolic conditions via modulation of GI bitter taste receptor-mediated hormone release
Treatment or prevention of metabolic diseases such as obesity and diabetes by modulating hormone release using GI bitter taste receptor ligands, including ligands conjugated with complementary molecules, administered enterally.
The claims cover methods, compositions, and systems for modulating metabolic hormone release from GI cells via administering GI bitter taste receptor ligands, including conjugated ligands designed to reduce systemic absorption, delivered enterally to treat metabolic conditions by targeting receptors and selectively inducing hormone secretion.
Stated Advantages
Allows modulation of GI bitter taste receptor activity and consequent metabolic hormone release.
Provides targeted control of hormone release related to metabolic diseases such as obesity and diabetes.
Minimizes systemic absorption of ligands to increase specificity and decrease adverse effects.
Enables combinations of ligands to achieve additive or synergistic effects on hormone modulation.
Documented Applications
Medical treatment of metabolic diseases and conditions, including obesity and diabetes.
Biological analysis and diagnostics related to GI bitter taste receptor activity and hormone release.
Food processing, taste and flavor modulation, nutrition, and nutraceutical applications involving modulation of bitter taste receptors.
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