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US-20260125514-A1 - CROSSLINKED POLYMERS AND THEIR USES

US20260125514A1US 20260125514 A1US20260125514 A1US 20260125514A1US-20260125514-A1

Abstract

A composition including homogenous mixture of a polymer containing at least two free amino functional groups, and a compound having an aldehyde functional group, the compound being of formula (I) or formula (II) R1 is C5-C25 alkyl, having one or more double bonds, and/or one or more triple bonds, possibly branched. The stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3.

Inventors

  • Nathanaël GUIGO
  • Mohamed MEHIRI
  • Giuseppe MELILLI
  • Patricia Rousselle
  • Nicolas SBIRRAZZUOLI

Assignees

  • Université Côte d'Azur
  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
  • UNIVERSITÉ CLAUDE BERNARD LYON 1

Dates

Publication Date
20260507
Application Date
20231103
Priority Date
20221103

Claims (18)

  1. 1 - 17 . (canceled)
  2. 18 . A composition consisting essentially of a homogenous mixture of: a polymer containing at least two free amino functional groups, and a compound comprising an aldehyde functional group, said compound being of formula I or of formula II, wherein R1 is C5-C25 alkyl, having one or more double bonds, and/or one or more triple bonds, possibly branched, and wherein the stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3.
  3. 19 . The composition according to claim 18 , wherein the compound represents from 5 to 15% by weight of the composition.
  4. 20 . A structured network comprising or consisting essentially of a polymer containing at least two free amino functional groups operably crosslinked to compound comprising two aldehyde groups of formula II, wherein R1 is C5-C25 alkyl, having one or more double bonds, and/or one or more triple bonds, possibly branched, and wherein the stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3, or an hydrated form thereof.
  5. 21 . The structured network according to claim 20 , wherein the polymer containing at least two free amino functional groups is an animal or plant protein, a polysaccharide containing an amino group or an artificial amino polymer.
  6. 22 . The structured network according to claim 21 , wherein the animal or plant protein is chosen from gelatin, keratin, casein and lactoserum proteins, elastin, collagen, soy protein, serum bovine albumin, fibrin and fibrinogen, and resilin.
  7. 23 . The structured network according to claim 20 , wherein the compound of formula II is oxytoxin-2 of formula III
  8. 24 . The structured network according to claim 20 , wherein the polymer containing at least two free amino functional groups is chosen from gelatin and chitosan.
  9. 25 . The structured network according to claim 20 , wherein the compound represents from 5 to 15% by weight of the structured network.
  10. 26 . A method for lubricating a hydrophobic surface of a device, the method comprising applying either: i) a composition on the surface, the composition consisting essentially of a homogenous mixture of: a polymer containing at least two free amino functional groups, and a compound comprising an aldehyde functional group, said compound being of formula I or of formula II, wherein R1 is C5-C25 alkyl, having one or more double bonds, and/or one or more triple bonds, possibly branched, wherein the stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3, or ii) a structured network comprising or consisting essentially of a polymer containing at least two free amino functional groups operably crosslinked to compound comprising two aldehyde groups of formula II, wherein R1 is C5-C25 alkyl, having one or more double bonds, and/or one or more triple bonds, possibly branched, and wherein the stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3, or an hydrated form thereof
  11. 27 . A method for treating an animal wound, the method comprising applying a structured network according to claim 20 , onto a wound of the animal.
  12. 28 . A medical device comprising a surface, the medical device comprising a structured network according to claim 20 coated to the surface.
  13. 29 . The medical device according to claim 28 , said medical device being a wound dressing; a patch; a film; a wound filler; an hydrogel dressing; a skin substitute; an hydrocoilloid dressing or a foam; a carrier for cells, molecules, genes, bioactive compounds or nanoparticles; and a scaffold for organoid culture.
  14. 30 . A method for producing a structured network, the method comprising: mixing: a first organic solvent comprising a polymer containing at least two free amino functional groups; and a second organic solvent comprising a compound containing comprising 2 aldehyde groups of formula I, to obtain a mixture wherein the stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3, wherein said first organic solvent is miscible in said second solvent, contacting the mixture with a basic composition, to obtain a crosslinked mixture, possibly washing the crosslinked mixture, and recovering the crosslinked mixture which is in a form of a structured network.
  15. 31 . The method for producing a structured network according to claim 30 , wherein the mixture is poured in a recipient and cooled down to a temperature from 2° C. to 15° C., and wherein the polymer containing at least two free amino functional groups is gelatin.
  16. 32 . A structured network obtained or liable obtained by the method according to claim 30 .
  17. 33 . A kit comprising: a polymer containing at least two free amino functional groups as defined in claim 18 , and a compound of formula I wherein R1 is a C5-C25 terpen; and optionally an aqueous basic solution.
  18. 34 . A method for crosslinking polymer containing at least two free amino functional groups, in order to obtain a structured network, the method comprising contacting the polymer with a compound as defined in claim 18 , of formula I or of formula II.

Description

FIELD The invention relates to crosslinked polymers, and their uses in particular in therapy and treatments of human and animal body. BACKGROUND Tissue engineering involves the use of materials with suitable biochemical and physiological properties to replace, repair, regenerate biological tissues and/or enhance these processes. The particular tissue involved may have certain mechanical and structural requirements for proper functioning. There is a need for materials which are easily tunable for use with a particular target tissue and have suitable biochemical and physiological properties for tissue engineering. Polymer hydrogels have structural similarities to numerous macromolecular components in the human body, are generally considered biocompatible, and have been investigated extensively as materials useful for drug delivery, tissue repair and tissue engineering, as well as for use as surgical sealants and adhesives. With increasing frequency, polymer hydrogels are designed for in situ gelation from a liquid precursor, thereby allowing minimally invasive administration via syringe or needle. Existing hydrogel systems, formed chemically or physically, are subject to several limitations. Chemically cross-linked hydrogels often employ toxic cross-linking agents and/or radicals, and the resulting hydrogels are often non-biodegradable. On the other hand, physical hydrogels—formed through ionic interactions, hydrophobic interactions, hydrogen bonding, or phase transition-—are relatively weak and can be prone to unwanted or uncontrollable degradation through ion exchange, ion diffusion, or monomer dissolution. An alternate approach—solidification by enzymatic cross-linking-—has two principal advantages, compared to other hydrogel systems. First, an enzyme has substrate specificity to allow controllable gel formation. Second, an enzymatic method can be applied to the in vivo utilization of cross-linked hydrogels, under appropriate physiological conditions. A particular biopolymer for use in medical applications is disclosed in U.S. Pat. No. 6,132,759, which relates to a medicament containing a biopolymer matrix comprising gelatin cross-linked with oxidized polysaccharides. The biopolymer of this patent is claimed to be useful for treating skin wounds or dermatological disorders. However, use of non-natural crosslinker is not required. Biomass and biomass-derived products have attracted a lot of attention as potential precursors for a wide variety of bio-based materials, but also for the appeal of natural platform molecules that can also offer a great combination of strategies to design innovative bioinspired functional materials. Among the different algal bioresources, some of them-mainly macroalgae—are still under-exploited while they can be highly invasive, which can lead to ecological problems. Therefore, there is a need to provide new bio-based materials, useful for animal and human application, avoiding chemistry based-compound. SUMMARY One aim of the invention is to provide a new and easy process to produce bio-based gel, that is biocompatible for animal and human application. Other aim of the invention is to provide medical and non-medical application of this gel. Still another aim of the invention is to provide a process for producing such a gel. Thus, the invention relates to a composition, preferably isolated, comprising, comprising essentially, or consisting of a homogenous mixture of: a polymer containing at least two free amino functional groups, anda compound comprising an aldehyde functional group, said compound being of formula I or of formula II, wherein R1 is C5-C25 alkyl, having one or more double bonds, and/or one or more triple bonds, possibly branched,wherein the stoichiometric ratio between the aldehyde functional group contained in the compound and the amino functional groups contained in the polymer is from 0.1 to 3. BRIEF DESCRIPTION OF THE DRAWINGS The invention will be better understood in view of the following drawings and examples FIG. 1 represent photos of crosslinked gelatin hydrogels obtained with a concentration of 5 wt % (A), 10 wt % (B) or 15 wt % (C) Caulerpenyne (CYN). FIG. 2 represents microscopic photos of (A) un-crosslinked gelatin, and (B and C) gelatin crosslinked with 5 or 10% Caulerpenyne, respectively. Neat gelatin was processed in the same way without adding CYN. The hydrogel so obtained was referred to uncrosslinked gelatin. FIG. 3 represents a graph showing the hydrolysis rate (in %) over the time in months, of networks crosslinked with 5 wt % (square), 10 wt % (circle) and 15 wt % (triangle) caulerpenyne (CYN). FIG. 4 represents a graph showing the sweeling degree (%) of networks crosslinked with 5% (A), 10% (B) and 15% (C) caulerpenyne (CYN). FIG. 5 is a graph showing fibroblast growth (OD at 590 nm) over the time (in hours) when seeded on plates coated with gelatin (A) or reticulated gelatin with 5 wt % (α-curve with square), 10 wt % (C-curve with triangles) o