Polysaccharide Retinoid Conjugates for Sustained Delivery

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Solution Overview

Problem

Current treatments for retinoid deficiency lack effective methods for sustained delivery and absorption, leading to inadequate treatment of retinal diseases associated with inadequate production of 11-cis-retinal.

Innovation Solution

Polysaccharide therapeutic conjugate compositions are developed, where a retinoid is covalently linked to a monosaccharide subunit of a polysaccharide with a hydrolysable covalent linkage, allowing controlled, delayed, or sustained release upon enteral administration, effectively providing therapeutic levels of retinoids for extended periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If retinoids are complexed with soluble proteins or esterified with long-chain fatty acids for protection and storage, then absorption and toxicity reduction are improved, but controlled and sustained delivery over extended periods cannot be achieved

Engineering Contradiction:

Improveabsorption and toxicity reductionVSAvoidduration of therapeutic delivery

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent employs a composite material system consisting of retinoid molecules covalently linked to polysaccharide chains. This composite structure combines the therapeutic properties of retinoids with the controlled release capabilities of polysaccharides, enabling sustained delivery over periods of hours to weeks while maintaining absorption efficiency and reducing toxicity through the hydrolysable linkage mechanism.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent utilizes changes in the chemical environment (pH, enzymatic conditions) to trigger hydrolysis of the covalent linkage between retinoid and polysaccharide. This parameter-based control allows the therapeutic agent to be released in a controlled manner over extended periods, transforming the delivery timeline from immediate to sustained without compromising absorption or increasing toxicity.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If retinoids are administered to provide therapeutic levels for sustained treatment, then treatment effectiveness is improved, but frequent continuous administration is required

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidadministration frequency

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary action by pre-linking the retinoid therapeutic agent to the polysaccharide carrier through hydrolysable covalent linkages before administration. This pre-prepared conjugate structure is designed to release the therapeutic agent gradually in vivo, eliminating the need for frequent re-administration while maintaining effective therapeutic levels over extended periods.

Inventive Principle:

Principle #10Preliminary action

3Duration of action of moving object

If covalent linkages are used to link retinoid to polysaccharide, then sustained delivery is achieved, but the linkages must be degradable by hydrolysis during digestion

Engineering Contradiction:

Improvesustained delivery periodVSAvoidsynthesis complexity with phase transfer catalyst

Core Design Contradiction:

Duration of action of moving objectVSEase of manufacture

Solution Approach 1:

The patent introduces a phase transfer catalyst as an intermediary substance to facilitate the covalent bonding between retinoid and polysaccharide during synthesis. This catalyst enables the formation of hydrolysable linkages under controlled conditions, making the manufacturing process feasible despite the complexity of creating degradable covalent bonds that will later release the therapeutic agent through hydrolysis in the digestive system.

Inventive Principle:

Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The polysaccharide conjugate compositions ensure sustained delivery of retinoids, improving photoreceptor function and treating retinal diseases by maintaining therapeutic levels of retinoids for hours to weeks without continuous administration, as demonstrated in animal models like Lrat−/− mice.

Implementation Method 1

The linkage is degradable by hydrolysis during digestion of the composition to provide controlled release, delayed release, and/or sustained delivery of the therapeutic agent

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

The phase transfer catalyst catalyzes the formation of a hydrolysable carboxylic ester covalent linkage between the monosaccharide subunit and the at least one retinoid

Methodology Applied

Scientific EffectCatalysis: Catalysis

Data Source

PatentUS11065338B2Polysaccharide therapeutic conjugates

Publication Date: 2021.07.20 CASE WESTERN RESERVE UNIV

AI summary

A composition includes a polysaccharide at least one retinoid linked to at least one monosaccharide subunit of the polysaccharide with a covalent linkage. The linkage being degradable by hydrolysis during digestion of the composition to provide controlled, delayed, and/or sustained delivery of the at least one retinoid upon enteral administration of the composition to a subject.