(S)-Pindolol Dual-Receptor Action for Cachexia Weight Loss and Fatigue

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Solution Overview

Problem

Cachexia, characterized by involuntary weight loss, fatigue, weakness, and psychological distress, is not effectively treated with nutritional intervention and is distinct from eating disorders, with existing treatments often associated with side effects like fatigue, particularly in chronic illnesses such as cancer and heart failure.

Innovation Solution

A pharmaceutical formulation comprising at least 90% of a single enantiomer of a combined beta-adrenergic antagonist and 5-HT1a partial agonist or antagonist, specifically (S)-pindolol and its salts, which interacts with both beta-adrenergic and 5-HT1a receptors to reduce fatigue and promote weight gain without significant alterations in blood pressure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If conventional beta-adrenergic antagonists are used to treat cachexia, then weight loss is reduced, but fatigue is induced as a side effect

Engineering Contradiction:
Improveweight lossVSAvoidfatigue side effect
Core Design Contradiction:
Loss of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent combines two pharmacological actions into a single compound: beta-adrenergic antagonism (for reducing weight loss) and 5-HT1A partial agonism (for reducing fatigue). This merging of functions into one molecule allows simultaneous treatment of both the primary symptom and the side effect, resolving the contradiction between weight loss reduction and fatigue induction

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent changes the pharmacological parameters of the beta-blocker by selecting specific compounds with dual activity profiles. The chosen compounds have specific binding affinities for both beta-adrenergic receptors and 5-HT1A receptors, altering the traditional single-target parameter to a multi-target parameter profile that achieves both weight loss reduction and fatigue mitigation

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If nutritional intervention is used to treat cachexia, then simple and safe treatment is provided, but treatment effectiveness is insufficient

Engineering Contradiction:
Improvetreatment simplicityVSAvoidtreatment effectiveness
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent transitions from non-pharmacological intervention (nutrition) to pharmacological intervention with a specific mechanism of action. By changing the treatment modality parameter from dietary to medicinal, and selecting compounds with proven dual-receptor activity, the treatment achieves both simplicity of administration and proven effectiveness through targeted biological mechanisms

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If existing cachexia treatments are used, then some symptomatic relief is achieved, but significant side effects occur

Engineering Contradiction:
Improvesymptomatic reliefVSAvoidside effects
Core Design Contradiction:
Ease of operationVSObject-generated harmful factors

Solution Approach 1:

The patent merges the therapeutic effect with the side effect management into a single pharmacological agent. The dual-action compound provides symptomatic relief for cachexia while simultaneously counteracting the fatigue side effect that plagues conventional treatments, thereby improving the benefit-risk profile without complicating the treatment regimen

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP2359822B1Treatment of cachexia
Publication Date: 2016.08.03 AKAMIS BIO LTD

AI summary

The present invention provides a means for prevention and treatment of cachexia and other chronic illnesses including but not limited to the promotion of weight gain, reduction or prevention of weight loss by administration of a substance that both reduces the sensitivity of beta-adrenergic receptors and of 5-HT1a receptors. (S)-pindolol, (S)-propranolol, tertatolol or bopindolol are preferred for this purpose.