GHB Prodrug Compounds for Extended Release and Lower Dosing
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Solution Overview
Problem
Current GHB pharmaceutical preparations require high doses due to suboptimal pharmacokinetics and oral bioavailability, necessitating divided dosing, which is inconvenient for patients.
Innovation Solution
Development of GHB delivering compounds, including prodrugs and precursors, that offer improved bioavailability and/or longer duration of action, allowing for lower molar doses and potentially single-dose administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of GHB are administered to achieve therapeutic effect, then the therapeutic effect is improved, but the dosage complexity and patient burden increase due to required divided dosing
Solution Approach 1:
The patent applies preliminary action by developing prodrugs that are converted to active GHB in the body. The prodrugs are designed to be metabolized into GHB, thereby delivering the therapeutic agent in a form that requires lower initial dosing and potentially allows for less frequent administration. This resolves the contradiction by preparing the therapeutic effect through metabolic conversion rather than direct high-dose administration.
Solution Approach 2:
The patent employs parameter changes by modifying the chemical structure of GHB into various prodrug forms (esters, amides, carbamates) with different pharmacokinetic properties. These structural modifications change parameters such as oral bioavailability, half-life, and metabolic stability, enabling therapeutic effects at lower doses and potentially reducing dosing frequency, thus improving dosing convenience while maintaining reliability.
2Reliability
If high doses of GHB are administered, then therapeutic plasma concentrations are achieved, but oral bioavailability remains suboptimal
Solution Approach 1:
The patent uses intermediaries by introducing prodrug molecules that serve as carriers for GHB. These prodrugs are designed to have improved oral bioavailability and are metabolized in the body to release active GHB. The prodrug acts as an intermediary that facilitates better absorption and delivery of the therapeutic agent, resolving the contradiction between achieving therapeutic plasma concentrations and improving oral bioavailability.
Solution Approach 2:
The patent applies parameter changes by chemically modifying GHB into prodrugs with altered pharmacokinetic parameters. The prodrug structures (including various esters, amides, and carbamates) are designed to improve oral absorption, extend half-life, and enhance metabolic stability. These parameter changes enable achievement of therapeutic plasma concentrations with improved oral bioavailability, reducing the quantity of substance needed.
3Duration of action of moving object
If divided dosing is required to maintain therapeutic effect, then the therapeutic effect is sustained, but treatment complexity and patient burden increase
Solution Approach 1:
The patent applies preliminary action by designing prodrugs with extended half-lives and sustained release characteristics. These prodrugs are metabolized to release GHB over an extended period, maintaining therapeutic effects for longer durations. This allows for reduced dosing frequency and simplified treatment regimens while sustaining therapeutic effects, thereby resolving the contradiction between duration of action and treatment complexity.
Solution Approach 2:
The patent employs continuity of useful action by developing prodrugs that provide sustained release of active GHB. The prodrug structures are designed to be metabolized continuously, maintaining therapeutic plasma concentrations over extended periods. This continuous delivery mechanism sustains therapeutic effects without requiring frequent divided dosing, reducing treatment regimen complexity while maintaining duration of action.
Data Source
AI summary
Disclosed are one or more compounds comprising chemically modified gamma-hydroxybutyrate (GHB), 2-hydroxytetrahydrofuran, and/or 1,4-butanediol, and salts of such compounds (GHB delivering compounds and salts thereof). Also disclosed are compositions comprising at least one GHB delivering compound, or a salt thereof, methods of making such compounds, and methods of using such GHB delivering compounds and compositions. Methods of treatment using the compounds are also disclosed.