Esterified THC Prodrugs for Oral Bioavailability and Longer Half-Life
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Solution Overview
Problem
The low oral bioavailability and short half-life of tetrahydrocannabinol (THC) limit its therapeutic effectiveness and increase toxic and side effects, necessitating improved absorption, distribution, and metabolism to enhance bioavailability and selectivity on target sites.
Innovation Solution
Development of tetrahydrocannabinol derivatives, stereoisomers, solvates, pharmaceutically acceptable salts, or cocrystals that can be converted into parent drugs after ingestion, offering higher bioavailability and longer half-life with reduced toxic and side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If THC is used as a medicament, then therapeutic effects are achieved, but oral bioavailability is low (4%-12%)
Solution Approach 1:
The patent modifies the chemical structure of THC by introducing ester groups at different positions (forming compounds with formulas I, II, and III), thereby changing the physical and chemical parameters of the molecule. This structural modification improves oral bioavailability while maintaining therapeutic effects, as the derivatives are converted to parent drugs in vivo after ingestion.
2Reliability
If THC is administered, then therapeutic effects are achieved, but half-life is short
Solution Approach 1:
The patent employs prodrug design where the THC derivatives are prepared in advance with ester groups that will be hydrolyzed in vivo to release the active parent drug. This preliminary modification allows the compound to be more stable and have longer half-life during circulation, while still achieving therapeutic effects after metabolic conversion.
3Reliability
If THC dosage is increased to improve therapeutic effects, then therapeutic effectiveness increases, but toxic and side effects increase
Solution Approach 1:
The patent uses esterified THC derivatives as intermediary compounds that are more favorable for absorption and distribution. These prodrugs act as mediators that improve the drug's pharmacokinetic properties, allowing lower dosages to achieve the same therapeutic effect with reduced toxicity and side effects.
Data Source
AI summary
The present invention relates to tetrahydrocannabinol derivatives and medical use thereof, in particular to pyrimidine derivates represented by general formula (I), or stereoisomers, solvates, metabolites, pharmaceutically acceptable salts or cocrystals thereof, wherein the definitions of substituents in general formula (I) are the same as those in the description