pH-Responsive Polylactic Acid Micelles for Drug Solubility

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for solubilizing poorly water-soluble drugs using surfactants or polymeric micelles face issues such as adverse side effects, low stability, and non-biodegradability, particularly when administered orally or parenterally, and polylactic acid derivatives with molecular weights below 2,000 Daltons are not dissolvable in aqueous solutions at pH 4 or more.

Innovation Solution

Polylactic acid derivatives with molecular weights between 500 and 2,000 Daltons, capable of forming micelles in aqueous solutions at pH 4 or above, are synthesized by polycondensing 2-hydroxy carboxylic acid derivatives at elevated temperatures under reduced pressure, allowing for the entrapment and solubilization of poorly water-soluble drugs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional surfactants are used to solubilize poorly water-soluble drugs, then drug solubility is improved, but adverse side effects and low stability occur

Engineering Contradiction:

Improvedrug solubilityVSAvoidmicelle stability

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical structure parameters of the surfactant by using polylactic acid derivatives with specific molecular weights (500-2000 Daltons) and incorporating hydrophilic blocks with specific sequences (e.g., polyethylene glycol, polyoxyethylene) to improve micelle stability while maintaining drug solubility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite micellar structures by combining polylactic acid derivatives with hydrophilic blocks (such as polyethylene glycol or polyoxyethylene chains) to form diblock or multiblock copolymers that exhibit both biodegradability and enhanced stability

Inventive Principle:

Principle #40Composite materials

2Duration of action of stationary object

If polylactic acid derivatives with molecular weight below 2000 Daltons are used, then biodegradability is improved, but aqueous solubility at pH 4 or above is lost

Engineering Contradiction:

ImprovebiodegradabilityVSAvoidaqueous solubility

Core Design Contradiction:

Duration of action of stationary objectVSQuantity of substance

Solution Approach 1:

The patent applies local quality modification by incorporating hydrophilic blocks with specific sequences (e.g., polyethylene glycol, polyoxyethylene) into the polylactic acid derivative structure at specific positions to enhance aqueous solubility while maintaining the biodegradable polylactic acid backbone

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent creates composite polymer structures by combining biodegradable polylactic acid with hydrophilic blocks (such as polyethylene glycol or polyoxyethylene chains) to form diblock or multiblock copolymers that simultaneously exhibit biodegradability and enhanced aqueous solubility

Inventive Principle:

Principle #40Composite materials

3Reliability

If crosslinked polymeric micelles are used to improve stability, then micelle stability is improved, but biodegradability is lost

Engineering Contradiction:

Improvemicelle stabilityVSAvoidbiodegradability

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent introduces dynamic characteristics to the micelle structure by using reversible non-covalent interactions (hydrogen bonding, van der Waals forces, hydrophobic effects) that allow the micelle to maintain stability during circulation but dynamically disassemble and degrade in the biological environment, unlike permanent crosslinks

Inventive Principle:

Principle #15Dynamics

Data Source

PatentUS8778322B2pH responsive biodegradable polylactic acid derivatives forming polymeric micelles and uses thereof for poorly water soluble drug delivery

Publication Date: 2014.07.15 SAMYANG HLDG CORP

AI summary

Polylactic acid derivatives capable of forming micelles in an aqueous solution with a pH of 4 or above, having one terminal carboxyl group. The polylactic acid derivatives may be applied as a drug delivery system in various forms since poorly water soluble drugs can be entrapped inside the micelles.