Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Reexamination Certificate
2000-09-19
2004-06-15
Sellers, Robert (Department: 1712)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
C516S077000, C525S279000, C525S280000, C525S294000, C525S296000, C525S299000, C525S303000, C525S329500, C525S409000
Reexamination Certificate
active
06750298
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention generally relates to a novel family of biocompatible surfactant copolymers having a large spectrum of uses, notably in the pharmaceutical field, and for synthesizing materials in the dispersed state, as well as treating the surface of materials and biomaterials.
More particularly, the object of the present invention is surfactant biocompatible copolymers comprising one or more sequences having hydrophobic character which are constituted mainly of recurring units or non-recurring units of general formula defined below, in particular forming a poly(methylidene malonate).
Surfactant copolymers formed from one or more sequences having a hydrophilic character and one or more sequences having a hydrophobic character have been known for a long time.
In particular, the products constituted of polyoxyethylene sequences having hydrophilic character and polyoxypropylene sequences having hydrophobic character and marketed under the designation PLURONIC® are commonly used for preparing compositions for cosmetic or pharmaceutical use.
The main drawback of these copolymers comes from the fact that they comprise no biodegradable sequence.
Surfactant copolymers comprising biodegradable sequences have already been described for example in the EP 583 955 document. These are block copolymers which contain ethylene oxide units and units derived from amino acids, as hydrophobic sequences.
The biodegradability of these known copolymers is accompanied by a cleavage of the main chain.
SUMMARY OF THE INVENTION
It has been discovered, and this constitutes the basis of the present invention, a novel family of biocompatible surfactant copolymers which are biodegradable via a mechanism of bio-erosion which does not significantly modify the degree of polymerisation of said copolymer.
More specifically, the copolymers in accordance with the invention can degrade chemically or biochemically by cleavage of the lateral substituents constituting the sequences having hydrophobic character, and this bio-erosion is advantageously accompanied by the passage of a copolymer having the characteristics of a surfactant into an entirely hydrophilic copolymer of the same degree of polymerisation as the staring polymer.
The copolymers in accordance with the present invention have very many advantages over the surfactant copolymers known to date, these advantages result from the particular chemical structure of their sequences having hydrophobic character.
These sequences notably enable providing copolymers which have various structures, block structures or grafted structures, it being difficult for the latter structures to be accessible in the case of the copolymers described for example in the EP 583 955 document.
The high reactivity, in anionic polymerisation as well as in radical polymerisation, of the monomers used for preparing these sequences having hydrophobic character, facilitates adjusting the molecular masses of these sequences, and, consequently, the properties of the copolymers.
Finally, the copolymers in accordance with the present invention have, according to the chemical structure of their sequences having hydrophobic character, various degradation kinetics and are therefore suitable for a large range of applications.
DETAILED DESCRIPTION OF THE INVENTION
Thus, according to a first aspect, the present application aims to cover biocompatible copolymers of the type comprising at least one sequence having a hydrophilic character and at least one sequence having a hydrophobic character, characterised in that said sequence having hydrophobic character is formed:
either from a homopolymer constituted of recurring units of the following general formula (I):
in which:
R
1
represents an alkyl group having 1 to 6 carbon atoms or a (CH
2
)
m
—COOR
3
group in which m is an integer between 1 and 5 and R
3
represents an alkyl group having 1 to 6 carbon atoms;
R
2
represents an alkyl group having 1 to 6 carbon atoms; and
n is an integer between 1 and 5;
or from a random copolymer constituted of different recurring units of formula (I) as defined above;
or, finally, from a random copolymer constituted mainly of units of formula (I) as defined above.
Advantageously, the above-mentioned sequence having hydrophobic character will be formed from a homopolymer constituted of recurring units of formula (I) as defined above.
Without leaving the context of the present invention, this sequence having hydrophobic character can also be formed from a random copolymer constituted of different recurring units of formula (I) as defined above, or even from a random copolymer constituted mainly of units of formula (I) as defined above, i.e. constituted of at least 50%, expressed in molar proportions, of such units, it being possible for the other units to be formed from malonic, vinylic, or acrylic monomers which are copolymerisable with the methylidene malonate units of formula (I).
According to a currently preferred embodiment of the invention, the above-mentioned sequence having hydrophobic character is constituted of recurring units of the above-mentioned general formula (I) in which:
R
1
represents an alkyl group having 1 to 6 carbon atoms;
R
2
represents an alkyl group having 1 to 6 carbon atoms; and
n is a number equal to 1.
According to a particularly preferred embodiment of the invention, the above-mentioned sequence having hydrophobic character is formed from a homopolymer constituted of recurring units of formula:
According to a particular characteristic, the sequence having hydrophilic character of the biocompatible copolymers in accordance with the present invention is selected from a poly(oxyethylene), a poly(vinyl alcohol), a poly(vinylpyrrolidone), a poly(N-2 hydroxypropyl methacrylamide), a poly(hydroxyethyl methacrylate), a hydrophilic poly(amino acid) such as a polylysine, a polysaccharide, and will preferably be constituted of a poly(oxyethalene).
The copolymers in accordance with the present invention can have various structures, block structures or grafted structures.
These copolymers may generally be characterised:
by a content by weight of sequences having hydrophobic character of between 5 and 95%, preferably of between 10 and 90%;
by a total molar mass of the sequences having hydrophobic character between 1,000 and 80,000 g/mol, and preferably between 1,000 and 50,000 g/mol.
The copolymers in accordance with the present invention can be prepared by classical polymerisation techniques well known to the person skilled in the art.
Amongst these techniques, anionic polymerisation, radical polymerisation, or even the technique of coupling the precursor sequences of the copolymer, will preferably be used, these sequences having been adequately functionalised beforehand on the chain end.
The anionic polymerisation is more particularly suitable for preparing block copolymers.
The anionic copolymerisation comprises the sequential addition of the monomers and enables obtaining copolymers of perfectly defined structure, the amounts of initiators and monomers engaged enabling controlling the degree of polymerisation of each of the sequences.
Thus, a block copolymer can be obtained:
either by anionic polymerisation of a first monomer and reaction of the growing chain with a second monomer;
or by activation of a precursor polymer which will act as initiator for the polymerisation of a second monomer.
The initiator agents which can be used within the context of these anionic polymerisations will generally be:
on the one hand, organometallic derivatives, such as butyllithium, and diphenylhexyllithium in particular;
on the other hand, alkoxides, and in particular macromolecular alkoxides, such as a POE alkoxide, which can be generated by activation of a hydroxy function with the aid of cumylpotassium, diphenylmethylpotassium, or naphthalenepotassium.
The anionic polymerisation will generally be carried out in a solvent which is compatible with the various sequences of the copolymer.
In the case in which the sequence having hydrophilic character is constituted of a pol
Breton Pascal
Bru-Magniez Nicole
Couvreur Patrick
Larras Virginie
Riess Gerard
Dennison Schultz Dougherty & MacDonald
Sellers Robert
Virsol
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