New hydrogels having a silylated structure, and method for obtaining same

Patent metadata

Field	Value
Publication number	US-2018200408-A1
Application number	US-201615743319-A
Country	US
Kind code	A1
Filing date	Jul 7, 2016
Priority date	Jul 10, 2015
Publication date	Jul 19, 2018
Grant date	—

Abstract

The present invention relates to hydrogels prepared using silylated organic molecules (such as silylated biomolecules), a method for obtaining same, and uses thereof.

First claim

1 . A process for producing a hydrogel comprising the steps of:
a) sot-gel polymerization of at least one molecule of formula (I):

wherein:
n is an integer greater than or equal to 2;
A is a structural organic polymer, preferentially of synthetic origin which may be, for example, selected from proteins, peptides such as collagen derivatives, in particular the sequences comprising Pro-Hyp-Gly or Pro-Pro-Gly or Asp-Pro-Gly or Pro-Lys-Gly tripeptide repeats, self-assembly peptide sequences such as Arg-Ala-Asp-Ala (SEQ ID 4), oligoprolines, oligoalanines, polysaccharides, such as hyaluronic acid and derivatives thereof, oligonucleotides, C 1 -C 6 -alkylene-glycol polymers, or polyvinylpyrrolidone;
Xa is a chemical bond or a spacer group preferentially represented by a divalent radical derived from a saturated or unsaturated aliphatic hydrocarbon chain comprising from 1 to 10 carbon atoms, optionally intercalated with one or more structural linkers selected from arylene or fragments —O—, —S—, —C(═O)—, SO 2 or —N(R 1 )—, wherein said chain is unsubstituted or is substituted by one or more radicals selected from halogen atoms, a hydroxyl group, a C 1 -C 4 alkyl group, a benzyl group and/or a phenethyl group;
R 1 represents a hydrogen atom, an aliphatic hydrocarbon group comprising from 1 to 6 carbon atoms, a benzyl or a phenethyl;
Y 1 , Y 2 , Y 3 , which may be identical or different, each independently represents a hydrogen atom, a halogen atom, an —OR 2 group, an aryl or a saturated or unsaturated aliphatic hydrocarbon chain comprising from 1 to 6 carbon atoms optionally substituted by a halogen atom, an aryl group or a hydroxyl group;
R 2 represents a hydrogen atom, an aryl group or a saturated or unsaturated aliphatic hydrocarbon chain comprising from 1 to 6 carbon atoms;
wherein at least two Xa groups as defined above are linked to different attachment points on A;

b) mixing with water, optionally at the same time as step a); and
c) recovering the hydrogel.

2 . The process for producing a hydrogel according to claim 1 , characterized in that said process comprises the addition, at the same time as or subsequent to step a), of at least one type of molecule of formula (II):

wherein:
m is an integer greater than or equal to 1, preferentially equal to 1;
B is an active ingredient, preferentially a biomolecule or a fluorophore, which may be, for example, selected from a peptide, an oligopeptide, a protein, such as collagen, a deoxyribonucleic acid, a ribonucleic acid, a polysaccharide, such as a pectin, a chitosan, a hyaluronic acid, a polyarabinose and polygalactose polysaccharide, and a glycolipid;
Xb is a chemical bond or a spacer group preferentially represented by a divalent radical derived from a saturated or unsaturated aliphatic hydrocarbon chain comprising from 1 to 10 carbon atoms, optionally intercalated with one or more structural linkers selected from arylene or fragments —O—, —S—, —C(═O)—, SO 2 or —N(R 3 )—, wherein said chain is unsubstituted or is substituted by one or more radicals selected from halogen atoms, a hydroxyl group, a C 1 -C 4 alkyl group, a benzyl group and/or a phenethyl group;
R 3 represents a hydrogen atom, an aliphatic hydrocarbon group comprising from 1 to 6 carbon atoms, a benzyl or a phenethyl;
Z 1 , Z 2, Z 3, which may be identical or different, each independently represents a hydrogen atom, a halogen atom, an —OR 4 group, an aryl or a saturated or unsaturated aliphatic hydrocarbon chain comprising from 1 to 6 carbon atoms optionally substituted by a halogen atom, an aryl group or a hydroxyl group;
R 4 represents a hydrogen atom, an aryl group or a saturated or unsaturated aliphatic hydrocarbon chain comprising from 1 to 6 carbon atoms; and
wherein preferentially only one of the Z 1 , Z 2 , or Z 3 groups is a halogen atom or an OR 4 group.

3 . The process for producing a hydrogel according to claim 1 or 2 , characterized in that the sol-gel polymerization process is carried out at physiological pH or in that the hydrogel is formed in the presence of a sufficient amount of water so that the water content of the hydrogel is at least 50 wt.% relative to the total weight of the hydrogel formed.

4 . The process for producing a hydrogel according to any one of claims 1 to 3 characterized in that said hydrogel is polymerized on or in at least a first hydrogel as a support, thus resulting in a multi-layer hydrogel.

5 . A hydrogel that can be obtained by the process according to any one of claims 1 to 4 .

6 . The hydrogel according to claim 5 for therapeutic and/or surgical use, preferentially characterized in that said hydrogel allows the delivery and/or the transport of active molecules, or for use in vivo in tissue engineering which may, for example, be achieved by in situ polymerization of said hydrogel in a living organism following the casting or the injection of molecules of formula (I) and optionally (II) as defined in claim 1 or 2 .

7 . In vitro use of a hydrogel according to claim 5 , in tissue engineering.

Assignees

• Univ Montpellier
• Centre Nat Rech Scient

Inventors

• Martinez Jean
• Mehdi Ahmad
• Subra Gilles
• Jebors Said
• Echalier Cécile

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61L26/0066

  Medicaments; Biocides · CPC title

• C07F7/087

  Compounds of unknown structure containing a Si-O-Si sequence · CPC title

• C12N2533/30

  Synthetic polymers · CPC title

• A61L27/22

  Polypeptides or derivatives thereof {, e.g. degradation products} · CPC title