GPR119 Agonist Oral Bioavailability Bone Mass
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Solution Overview
Problem
Current GIP peptide agonists for treating osteoporosis have limited oral bioavailability, impacting patient compliance and effectiveness in increasing bone mass.
Innovation Solution
Administration of a GPR119 agonist, which acts on the GPR119 receptor to increase GIP levels, promoting bone formation and identified through in vitro methods using specific G protein-coupled receptors and vertebrate enteroendocrine cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If GIP peptide agonists are used to treat osteoporosis, then bone formation is promoted, but oral bioavailability is limited
Solution Approach 1:
The patent uses GPR119 receptor as an intermediary target. Instead of directly administering GIP peptide which has poor oral bioavailability, the invention administers GPR119 agonists that act as intermediaries to stimulate endogenous GIP secretion from K cells, thereby achieving the therapeutic effect indirectly with improved oral availability
Solution Approach 2:
The patent enables the body's own K cells to produce and secrete GIP in response to GPR119 agonist stimulation. This self-service mechanism allows the endogenous system to generate the active peptide locally, bypassing the need for external administration of GIP itself and thus overcoming the oral bioavailability limitation
2Reliability
If GIP peptide is administered to increase bone mass, then bone formation is stimulated, but patient compliance is impacted
Solution Approach 1:
GPR119 agonists serve as intermediaries that can be orally administered with good bioavailability, replacing the need for direct GIP peptide administration. This intermediary approach maintains the therapeutic benefit while improving ease of administration and patient compliance
Solution Approach 2:
The patent changes the molecular parameter from GIP peptide to GPR119 agonist, which has different physicochemical properties including better oral bioavailability. This parameter change allows the drug to be administered orally with improved patient compliance while still achieving the desired bone formation effect through endogenous GIP stimulation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The GPR119 agonist effectively increases GIP levels, stimulating bone formation and potentially treating or preventing conditions characterized by low bone mass, such as osteoporosis, with oral administration providing improved bioavailability.
Implementation Method 1
contacting a test compound with a host cell or with membrane of a host cell comprising a G protein-coupled receptor... determining the ability of the test compound to stimulate functionality of the G protein-coupled receptor
Implementation Method 2
The G protein-coupled receptor... wherein the ability of the test compound to stimulate functionality of the G protein-coupled receptor is indicative of the test compound being a GIP secretagogue
Data Source
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AI summary
The present invention relates to methods of using GPR119 receptor to identify compounds useful for increasing bone mass in an individual. Agonists of GPR119 receptor are useful as therapeutic agents for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. Agonists of GPR119 receptor promote bone formation in an individual.