CBDA Ester Derivatives for Heat-Stable Anti-Nausea Therapy

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Solution Overview

Problem

Cannabidiolic acid (CBDA) is highly unstable, especially when subjected to heat, limiting its therapeutic applications, and there is a need for a more stable analogue with similar or enhanced biological efficacy.

Innovation Solution

Ester derivatives of CBDA, such as HU-580, are developed, which provide increased stability and maintain or enhance the biological profile of CBDA, including 5-HT1A receptor activation and anti-nausea effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CBDA is used for therapeutic applications, then anti-nausea and anxiolytic effects are achieved, but stability is poor especially under heat

Engineering Contradiction:

ImprovestabilityVSAvoidtherapeutic efficacy

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of CBDA through esterification at the carboxylic acid group, creating derivatives with improved stability parameters while maintaining therapeutic parameters. Specifically, ester groups with different alkyl chains (methyl, ethyl, propyl, butyl) were synthesized to optimize the stability-efficacy balance, with the butyl ester showing superior stability and potency.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite molecular structures by combining the CBDA core structure with various ester groups. These composite molecules (ester derivatives) integrate the stabilizing effect of the ester functionality with the therapeutic activity of the CBDA scaffold, achieving both improved stability and maintained efficacy.

Inventive Principle:

Principle #40Composite materials

2Reliability

If ester derivatives of CBDA are synthesized, then stability is improved, but structural complexity increases

Engineering Contradiction:

ImprovestabilityVSAvoidmolecular structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the molecule into distinct functional segments: the CBDA core structure (containing the therapeutic pharmacophore) and the ester substituent (providing stability). This modular approach allows independent optimization of each segment's function while maintaining overall molecular integrity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by making a specific local modification to the CBDA molecule - esterification at the carboxylic acid group - while leaving the rest of the molecule intact. This localized change introduces stability without significantly altering the overall molecular complexity or the therapeutic core structure.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11440870B2Cannabidiolic acid esters compositions and uses thereof

Publication Date: 2022.09.13 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD

AI summary

Cannabidiolic acid esters, compositions comprising them and uses thereof in the treatment of various diseases, conditions and symptoms.