Amphiphilic polymer functionalized by methionine
The present invention relates to new amphiphilic polymers comprising hydrophobic groups and methionine groups. It also relates to compositions with a controlled release profile comprising such polymers, non-covalently combined with an active ingredient, in particular an active ingredient such as a peptide or a protein comprising in their sequence at least one amino acid which is sensitive to oxidation.
1 . Amphiphilic polymer comprising a hydrophilic backbone, wherein said backbone comprises at least one side group of methionine or methionine derivative, and comprises hydrophobic side groups distinct from said methionine or one of its derivatives.
2 . Polymer according to claim 1 , in which the at least one side group of methionine or methionine derivative and hydrophobic side groups are arranged randomly.
3 . Polymer according to claim 1 , wherein the hydrophilic backbone is a polymer or copolymer selected from the group of: polyamino acids, polysaccharides, polyacrylates and polymethacrylates.
4 . Polymer according to claim 1 , wherein the hydrophilic backbone is a polyamino acid selected from the group of: poly(glutamic acid), poly(aspartic acid), the polylysines and their copolymers.
5 . Polymer according to claim 1 , wherein said polymer has a methionine molar grafting rate varying from 0.5 to 20%.
7 . Polymer according to claim 1 , wherein the at least one side group of methionine or methionine derivative possess(es) one of the following structures:
in which:
Ra is selected from the group consisting of: a hydroxy, NH 2 , OMe, OEt, NHCH 3 and N(CH 3 ) 2 group,
Rb and Rc represent independently a hydrogen atom, a methyl or ethyl;
with when one of the groups Rb and Rc is a hydrogen atom, then the other group represents a C 1 to C 6 acyl group, and the configuration of the methionine can be L, D or a racemic mixture.
7 . Polymer according to claim 1 , said polymer comprising a hydrophobic groups molar grafting rate varying from 2 to 30%.
8 . Polymer according to claim 1 , wherein the hydrophobic group is selected from the groups comprising:
the linear or branched C 5 to C 30 alkyls,
the linear or branched C 5 to C 30 alkyls comprising at least one unsaturation and/or at least one heteroatom,
the C 8 to C 30 alkylaryls or arylalkyls,
the C 8 to C 30 alkylaryls or arylalkyls comprising at least one unsaturation and/or at least one heteroatom,
the C 10 to C 30 (poly)cyclics, and
the C 10 to C 30 (poly)cyclics optionally comprising at least one unsaturation and/or at least one heteroatom.
9 . Polymer according to claim 1 , wherein said hydrophilic backbone is a sodium poly(L)glutamate and the hydrophobic group a tocopheryl group of synthetic origin.
10 . Polymer according to claim 1 , wherein said methionine derivative is methionine amide or methionine ethyl ester.
11 . Polymer according to claim 1 , wherein said polymer has a molar mass by weight ranging from 2,000 to 200,000 g/mole.
12 . Polymer according to claim 1 , wherein said polymer comprises at least one graft of polyethylene glycol type.
13 . Polymer according to claim 1 , wherein said polymer is capable of spontaneously forming nanoparticles when dispersed in an aqueous medium with a pH ranging from 5 to 8.
14 . Nanoparticles of a polymer according to claim 1 , wherein the size of said polymer is between 1 and 1000 nm.
15 . Composition comprising a polymer according to claim 1 and at least one active ingredient selected from the group consisting of: oxidation-sensitive protein and oxidation-sensitive peptide.
16 . Composition according to claim 1 , wherein said protein or peptide contains at least one methionine in its sequence.
17 . Composition according to claim 15 wherein said composition is in the form of nanoparticles, microparticles, gels or films.
18 . Composition according to claim 15 , wherein the release profile of said active ingredient is regulated as a function of time.