Enzyme-Cleavable Oxycodone Prodrug Controlled Release
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Solution Overview
Problem
Ketone-containing opioids like hydrocodone and oxycodone are prone to misuse, abuse, and overdose, and existing control measures are costly and often ineffective, leading to denial of treatment for patients and substantial morbidity and social consequences.
Innovation Solution
Development of Compound KC-7, a ketone-modified opioid prodrug that provides controlled release of oxycodone through enzyme cleavage followed by intramolecular cyclization, combined with a trypsin inhibitor to regulate enzymatic cleavage and attenuate drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ketone-containing opioids like oxycodone are made accessible for patient treatment, then pain management efficacy is improved, but risk of misuse, abuse, and overdose increases
Solution Approach 1:
The patent applies preliminary action by converting oxycodone into a prodrug form (Compound KC-7) that requires enzymatic conversion in the body to release the active opioid. This pre-modification ensures the drug cannot be misused in its administered form, while still providing effective pain management after proper metabolic conversion.
Solution Approach 2:
The patent uses an intermediary mechanism by introducing a promoiety with enzyme-cleavable moiety that acts as a mediator between the administered prodrug and the active oxycodone. This intermediary structure enables controlled release through enzymatic cleavage followed by intramolecular cyclization, preventing direct misuse while maintaining therapeutic efficacy.
2Object-affected harmful factors
If controlled release mechanisms are implemented to prevent misuse, then safety is improved, but treatment accessibility deteriorates
Solution Approach 1:
The patent applies self-service by designing a prodrug system that automatically converts to active oxycodone through the patient's own enzymatic processes in the body. The enzyme-cleavable moiety and cyclizable spacer leaving group work together to self-regulate drug release without requiring external monitoring or intervention, maintaining accessibility while preventing misuse.
Solution Approach 2:
The patent uses parameter changes by modifying the chemical structure of oxycodone to create a prodrug with specific enzyme-cleavable moieties and cyclizable spacers. These structural parameter changes enable controlled release kinetics that prevent misuse while ensuring proper activation in the body, balancing safety with treatment accessibility.
3Manufacturing precision
If enzyme-cleavable prodrug design is used to control release, then drug delivery precision is improved, but complexity of the compound structure increases
Solution Approach 1:
The patent applies segmentation by dividing the prodrug structure into distinct functional segments: the oxycodone core, the enzyme-cleavable moiety, and the cyclizable spacer leaving group. This segmentation allows each component to perform its specific function while maintaining overall structural manageability and enabling precise controlled release through enzymatic cleavage followed by cyclization.
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
Compound KC-7 offers efficient and controlled delivery of oxycodone, reducing the risk of misuse and overdose by modulating drug release, thereby improving treatment accessibility and efficacy while minimizing adverse effects.
Implementation Method 1
the promoiety comprises an enzyme-cleavable moiety and a cyclizable spacer leaving group such that Compound KC-7 provides controlled release of oxycodone via enzyme cleavage followed by intramolecular cyclization
Data Source
AI summary
The embodiments provide Compound KC-7, N-1-[(S)-2-(oxycodone-6-enol-carbonyl-methyl-amino)-2-carbonyl-sarcosine-ethyl amine]-arginine-glycine-acetate, or acceptable salts, solvates, and hydrates thereof. The present disclosure also provides compositions, and their methods of use, where the \compositions comprise a prodrug, Compound KC-7, that provides controlled release of oxycodone. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of oxycodone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.