Buprenorphine Ester Derivatives for Opiate Dependence
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Solution Overview
Problem
Current buprenorphine treatments for opiate abuse and dependence have limitations, including low bioavailability, potential for misuse, and restrictive administration routes, which hinder effective and safe management of opiate dependence and pain relief.
Innovation Solution
Development of buprenorphine ester derivatives with modified phenolic hydroxyl groups, which can be administered in various forms, including solid dosage forms, to enhance bioavailability, duration of action, and reduce misuse potential, allowing for convenient and flexible administration routes such as oral, sublingual, and transdermal delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If buprenorphine is administered orally, then it is easy to administer, but bioavailability is low (approximately 5%)
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of buprenorphine through esterification of the phenolic hydroxyl group. This chemical modification changes the physicochemical parameters of the molecule, specifically improving its lipophilicity and enabling it to bypass first-pass metabolism, thereby achieving high oral bioavailability (greater than 50%) while maintaining ease of oral administration.
2Reliability
If buprenorphine is administered sublingually, then bioavailability is high (approximately 50%), but administration is restrictive and requires patient compliance
Solution Approach 1:
The ester derivatives modify the absorption parameters of buprenorphine, allowing it to be effectively administered orally with bioavailability exceeding 50%, eliminating the need for restrictive sublingual administration and improving patient compliance while maintaining high bioavailability.
3Reliability
If buprenorphine is used for treatment, then it provides effective pain relief and opiate dependence treatment, but it has potential for misuse
Solution Approach 1:
The patent applies preliminary action by incorporating disulfiram or its metabolites into the pharmaceutical composition before administration. This preliminary inclusion creates a deterrent effect against misuse, as co-administration of opioids with disulfiram produces unpleasant reactions, thereby reducing misuse potential while preserving the therapeutic effectiveness of buprenorphine for legitimate medical use.
4Duration of action of moving object
If buprenorphine has long duration of action, then dosing interval can be extended, but this requires sufficient duration to enable single daily dose
Solution Approach 1:
The ester derivatives of buprenorphine modify the pharmacokinetic parameters of the drug, extending its duration of action. This allows for extended dosing intervals, enabling treatment to be administered as a single daily dose or even less frequently, thereby improving productivity by reducing the number of dosing events while maintaining therapeutic effectiveness.
Data Source
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AI summary
Ester derivatives of the phenolic hydroxyl group of buprenorphine are described that can be used in the treatment of opiate dependency and/or moderate to severe pain. The esters have an enhanced bioavailability, an enhanced duration of action, and a reduced abuse potential.