Oral GPCR Conjugates for Bioavailability and Half-Life Extension
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Solution Overview
Problem
Existing oral drug formulations face challenges with poor bioavailability due to first-pass metabolism and high protein binding, limiting the efficacy and therapeutic effect of GPCR agonists and antagonists in treating conditions like type 2 diabetes, obesity, osteoporosis, and neurological disorders.
Innovation Solution
Development of compounds comprising GPCR agonists or antagonists covalently bound to oral bioavailability and protein binding enhancing moieties, such as bile salts, fatty acids, and lipophilic compounds, to enhance absorption and prolong circulating half-life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If GPCR agonists or antagonists are administered orally, then ease of operation is improved, but bioavailability deteriorates due to first-pass metabolism
Solution Approach 1:
The patent applies composite materials by conjugating GPCR agonists or antagonists with bile salts to create a hybrid molecule that combines the therapeutic activity of the GPCR ligand with the oral absorption-enhancing properties of bile salts, thereby resolving the contradiction between ease of oral administration and poor bioavailability
Solution Approach 2:
The patent changes the chemical parameters of the GPCR agonist/antagonist by modifying its structure through conjugation with bile salts, which alters its pharmacokinetic properties including oral bioavailability and protein binding characteristics, enabling improved oral delivery
2Ease of operation
If GPCR agonists or antagonists are administered orally, then ease of operation is improved, but therapeutic effect deteriorates due to low bioavailability
Solution Approach 1:
The conjugation of GPCR agonists/antagonists with bile salts creates a composite structure that simultaneously enables oral administration and maintains therapeutic efficacy by improving bioavailability through enhanced intestinal absorption and reduced first-pass metabolism
3Productivity
If GPCR agonists or antagonists are administered, then therapeutic effect is improved, but duration of action deteriorates due to rapid clearance
Solution Approach 1:
The patent uses composite material strategy by conjugating GPCR agonists/antagonists with bile salts to create a molecular hybrid that prolongs circulating half-life through enhanced protein binding, thereby extending duration of action while maintaining therapeutic effect
Solution Approach 2:
The conjugation modifies the pharmacokinetic parameters of the GPCR ligand, specifically increasing protein binding affinity and reducing clearance rate, which extends the circulating half-life and duration of therapeutic action
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 modified compounds exhibit increased oral bioavailability and protein binding, leading to enhanced therapeutic effects and prolonged activity of GPCR agonists and antagonists in treating conditions like type 2 diabetes, obesity, osteoporosis, and neurological disorders.
Implementation Method 1
compounds comprising at least one GPCR agonist and/or antagonist and at least one oral bioavailability enhancing moiety and/or protein binding enhancing moiety
Implementation Method 2
compounds comprising at least one GPCR agonist and/or antagonist and at least one oral bioavailability enhancing moiety and/or protein binding enhancing moiety
Data Source
AI summary
Compounds comprising at least one GPCR agonist and/or antagonist and at least one oral bioavailability enhancing moiety and/or protein binding enhancing moiety, for treatment of GPCR agonist or antagonist responsive diseases and conditions via the oral route of administration, among other routes.