Stable Liquid Levodopa Composition for Continuous Subcutaneous Delivery

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Solution Overview

Problem

Current treatments for Parkinson's disease, primarily using levodopa, suffer from motor fluctuations and dyskinesia due to pulsatile dopaminergic stimulation, and existing formulations lack a stable liquid formulation suitable for continuous subcutaneous or transdermal delivery.

Innovation Solution

A pharmaceutically acceptable composition comprising carbidopa, at least 4% by weight levodopa, arginine, and optionally meglumine, with a pH of about 9.1 to 9.8, which forms a stable liquid formulation for continuous subcutaneous administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If levodopa is administered orally with standard formulations, then the treatment is simple and convenient, but the delivery is pulsatile leading to motor fluctuations and dyskinesia

Engineering Contradiction:

Improveconvenience of administrationVSAvoidcontinuity of dopaminergic stimulation

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent replaces the mechanical/oral administration system with a subcutaneous injection system using a stable liquid formulation. This substitution enables continuous delivery of levodopa and carbidopa, eliminating the pulsatile stimulation associated with oral dosing while maintaining treatment simplicity through a streamlined injection process.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the physical and chemical parameters of the levodopa formulation by creating a stable liquid composition with specific pH (9.1-9.8) and containing arginine and meglumine. This parameter change enables continuous subcutaneous administration, transforming the delivery pattern from pulsatile to continuous while improving therapeutic reliability.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If sustained-release oral levodopa formulations are used, then the convenience is maintained, but the formulations are no more efficacious than standard tablets

Engineering Contradiction:

Improveconvenience of administrationVSAvoidefficacy in reducing motor fluctuations

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent replaces the sustained-release oral formulation system with a subcutaneous injection system. This substitution achieves superior efficacy by enabling continuous delivery of levodopa and carbidopa, directly addressing the limitation of oral sustained-release formulations that fail to provide adequate efficacy in reducing motor fluctuations.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If intraduodenal or infusion methods are used for continuous levodopa administration, then motor complications are reduced, but the treatments are extremely invasive and inconvenient

Engineering Contradiction:

Improvecontinuity of levodopa deliveryVSAvoidinvasiveness and convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts the active ingredients (levodopa and carbidopa) into a stable liquid formulation suitable for subcutaneous administration. This extraction enables continuous delivery through a less invasive route compared to intraduodenal or infusion methods, reducing motor complications while improving ease of operation and patient convenience.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the formulation parameters by creating a stable liquid composition with pH 9.1-9.8 containing arginine and meglumine, enabling subcutaneous administration. This parameter change reduces invasiveness compared to intraduodenal or infusion methods while maintaining continuous delivery reliability.

Inventive Principle:

Principle #35Parameter changes

4Reliability

If large doses of levodopa are administered to overcome extracerebral metabolism, then the dopamine concentration in the brain is restored, but nausea and other side effects occur

Engineering Contradiction:

Improverestoration of brain dopamine concentrationVSAvoidnausea and side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent merges levodopa with carbidopa in a stable liquid formulation for continuous subcutaneous administration. This combination allows for lower levodopa doses to achieve the same therapeutic effect by preventing extracerebral metabolism, thereby restoring brain dopamine concentration while reducing nausea and other side effects.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20250114315A1Continuous administration of l-dopa, dopa decarboxylase inhibitors, catechol-o-methyl transferase inhibitors and compositions for same

Publication Date: 2025.04.10 NEURODERM LTD

AI summary

Provided herein, in part, is a method of treating a neurological or movement disorder in a patient in need thereof, comprising subcutaneously administering to said patient a pharmaceutically acceptable composition comprising levodopa and optionally carbidopa and optionally entacapone or tolcapone, or pharmaceutically acceptable salts thereof, wherein said composition is administered substantially continuously, and compositions that can be used in the disclosed methods.