Autocrosslinked Polysaccharides via Formamide Solvent Esterification
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Solution Overview
Problem
Existing polysaccharides, such as hyaluronan, chondroitin sulphate, heparan sulphate, and keratan sulphate, lack adjustable and reproducible rheological properties, particularly in terms of viscosity and viscoelasticity, which are crucial for various medical and cosmetic applications.
Innovation Solution
Development of acid autocrosslinked polysaccharides with concomitant presence of formate esters and esters between polysaccharide acid groups and non-polysaccharide carboxylic acids, allowing for modulated chemico-physical properties and viscoelastic behavior through a process involving reaction in protic solvent formamide with sodium or potassium salts and anhydrides, eliminating the need for costly and risky aprotic solvent-based transformations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If autocrosslinking is achieved using aprotic solvents (DMF, DMSO) with activated esters, then viscoelastic characteristics are induced, but the process becomes costly and involves safety risks
Solution Approach 1:
The invention changes the fundamental parameter of the reaction medium from aprotic solvents (DMF, DMSO) to water as the reaction medium. This parameter change eliminates the need for costly and potentially hazardous organic solvents while maintaining the ability to achieve autocrosslinking and induce viscoelastic characteristics in the polysaccharide derivatives.
Solution Approach 2:
The invention replaces expensive and potentially hazardous reagents (activated esters, aprotic solvents) with cheap, safe, and readily available alternatives (water as reaction medium, standard esterification reagents). This substitution maintains the desired technical effect while dramatically reducing manufacturing cost and safety risks.
2Ease of manufacture
If simple monoesterification is performed without crosslinking, then the process is simple, but viscoelastic properties are not achieved
Solution Approach 1:
The invention merges two previously separate processes (monoesterification and autocrosslinking) into a single simultaneous operation. The esterification reaction and autocrosslinking occur concurrently in the same reaction medium (water), achieving both structural modification and network formation without requiring separate processing steps.
Solution Approach 2:
The invention enables the polysaccharide to perform self-service by utilizing its own carboxyl groups to form autocrosslinks with alcoholic hydroxyls during the esterification process. This self-autocrosslinking mechanism occurs spontaneously under the reaction conditions without requiring external crosslinking agents or complex activation procedures.
3Adaptability or versatility
If the polysaccharide structure is modified to optimize characteristics, then application suitability improves, but the structural complexity increases
Solution Approach 1:
The invention applies local quality modification by selectively esterifying specific hydroxyl groups on the polysaccharide chains while maintaining the overall structural integrity. The esterification occurs at specific locations (alcoholic hydroxyls) without requiring complex global structural changes, thus achieving optimized characteristics with minimal structural complexity increase.
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 resulting derivatives exhibit adjustable and reproducible rheological properties, ranging from solutions to strong gels, with enhanced viscosity and resistance to applied forces, suitable for medical devices, dermo-cosmetic agents, and controlled drug release, demonstrating improved biotolerability and modulability.
Implementation Method 1
formation of autocrosslinking esters between the hydroxyls of the repetitive polysaccharide units and the carboxyls present in the polysaccharide
Implementation Method 2
the carbonyl carbon to be attached by a nucleophil (such as the -OH group of the monosaccharide units), with simultaneous detachment of X
Implementation Method 3
inducement of viscoelastic characteristics which did not exist in the starting polysaccharide
Data Source
Figure 1
Figure 2
Figure 3a~3b
AI summary
Acid polysaccharides characterised by the concomitant presence of partial esters with non-polysaccharide carboxylic acids and esters between the acid groups of the initial polysaccharide and the alcohol groups of the repetitive units, with the formation of crosslinking among the polysaccharide chains. Process for the preparation of these derivatives comprising the reaction, in homogenous phase in the protic, polar solvent formamide, of the salt of a monovalent inorganic cation of the selected carboxylated polysaccharide with an anhydride of an alkylcarboxylic acid in the presence of a basic catalyst containing an atom of trisubstituted nitrogen. The formamide hydrolysis leads to the formation of a formate ester.