Polysarcosine-Vitamin E Micelles for PEG-Free Solubility

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Solution Overview

Problem

Existing vitamin E derivatives, such as TPGS, suffer from poor water solubility, toxicity, and immunogenicity due to the inclusion of PEG, leading to reduced efficacy and stability in drug delivery systems.

Innovation Solution

Development of polysarcosine-vitamin E derivatives that are biodegradable, non-immunogenic, and amphiphilic, forming self-assembled particles like micelles to encapsulate active agents, offering improved solubility and antioxidant properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If PEG is included in vitamin E derivatives (TPGS) to improve water solubility, then solubility is improved, but immunogenicity and toxicity increase

Engineering Contradiction:
Improvewater solubilityVSAvoidimmunogenicity and toxicity
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The invention changes the chemical structure parameters by replacing PEG chains with polysarcosine chains in the vitamin E derivative structure. This structural parameter change maintains amphiphilic properties and water solubility while eliminating the immunogenicity and toxicity associated with PEG, as polysarcosine is biodegradable and non-immunogenic.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite material structure by combining vitamin E core with polysarcosine chains to form amphiphilic derivatives. This composite approach integrates the antioxidant properties of vitamin E with the biocompatibility and solubility enhancement of polysarcosine, achieving a material that overcomes the limitations of PEG-based derivatives.

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If PEG is used to achieve stealth properties and prolonged circulation time, then circulation time is improved, but accelerated blood clearance phenomenon occurs

Engineering Contradiction:
Improvecirculation timeVSAvoidcirculation time consistency
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The invention extracts and removes the PEG component from the vitamin E derivative structure, eliminating the source of the accelerated blood clearance phenomenon. By replacing PEG with polysarcosine chains, the derivative maintains solubility and biocompatibility without triggering the immunogenic response that causes ABC phenomenon and reduced circulation time consistency.

Inventive Principle:
Principle #2Taking out (Extraction)

3Stability of the object's composition

If vitamin E is esterified with acetate or succinate to improve shelf life, then stability is improved, but water solubility deteriorates

Engineering Contradiction:
Improveshelf lifeVSAvoidwater solubility
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The invention merges the stability-enhancing esterification approach with solubility-enhancing amphiphilic structure design. By combining vitamin E core with polysarcosine chains through ester or amide linkages, the derivative achieves both improved shelf life (through stable esterification) and enhanced water solubility (through amphiphilic structure with hydrophilic polysarcosine chains).

Inventive Principle:
Principle #5Merging (Combining)

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 polysarcosine-vitamin E derivatives demonstrate enhanced solubility and accumulation in the epidermis, overcoming the limitations of TPGS for skin delivery applications while maintaining therapeutic efficacy.

Implementation Method 1

forming self-assembled particles like micelles to encapsulate active agents

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

The polysarcosine-vitamin E derivatives of the invention are amphiphilic. They comprise a hydrophilic polar head portion, the PSar-based moiety, and a hydrophobic part, the vitamin E-based moiety.

Methodology Applied
Scientific EffectAmphiphilic properties: Amphiphiles

Implementation Method 3

the polysarcosine-vitamin E derivatives demonstrate enhanced solubility and accumulation in the epidermis

Methodology Applied
Scientific EffectSolubility enhancement: Solvation

Data Source

PatentEP4447936B1Polysarcosine-vitamin e derivatives
Publication Date: 2025.11.19 POLYPEPTIDE THERAPEUTIC SOLUTIONS SL
  • EP4447936B1 patent drawingFigure 1A~1B
  • EP4447936B1 patent drawingFigure 2
  • EP4447936B1 patent drawing

AI summary

It relates to a polymer comprising a repeating sarcosine-based unit which is covalently attached directly or through a linker to a vitamin E-based moiety, acceptable salts, stereoisomers and mixtures thereof, and to conjugates of formula (II) comprising these polymers. Nutraceutical, pharmaceutical, diagnostic and cosmetic compositions comprising the polymers and/or the conjugates of formula (II), together with acceptable excipients or carriers are also provided, as well as self-assembled particles comprising the polymers and/or the conjugates of formula (II) and optionally agents encapsulated within the self-assembled particles. It also relates to the use of the polysarcosine-vitamin E derivatives and/or their conjugates in medicine and diagnostics, and as solubilizers, absorption and permeation enhancers, emulsifiers or surface stabilizers.