Composition that can be cured by polymerisation for the production of biodegradable, biocompatible, cross-linkable polymers on the basis of polyvinyl alcohol
The present invention relates to a polymerization-curable composition for the preparation of biodegradable, biocompatible, cross-linked polymers on the basis of polyvinyl alcohol comprising: 5 to 100% by weight of (a) vinyl ester monomer(s) of one of the general formulas (I) to (III): wherein X is oxygen, sulfur, nitrogen, or phosphorus; n is 1 to 1000, at least 20% of the n being ≧2; the R 1 are selected from hydrogen; straight, branched or cyclic, saturated or unsaturated, n-valent hydrocarbon groups having 1 to 30 carbon atoms, which optionally have heteroatoms and are optionally substituted with one or more substituents selected from —OH, —COON, —CN, —CHO, and ═O, and n-valent radicals of biodegradable, biocompatible oligomers and polymers; m is an integer from 1 to 5; the R 2 are selected from hydrogen, —OH, ═O, and the options listed for R 1 ; and the R 3 are selected from hydrogen, —OH, and the options listed for R 1 ; 0 to 50% by weight of ethylenically unsaturated co-monomers; 0 to 10% by weight of (a) polymerization initiator(s); and 0 to 95% by weight of solvent(s).
1. A method for preparing a body implant comprising a biodegradable, biocompatible, cross-linked polymer, which method comprises the following steps:
providing a polymerization-curable composition comprising:
(a) 5 to 100% by weight of one or more vinyl ester monomers of the general formula (II):
wherein:
X is a heteroatom selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus;
n is 1 to 1000, at least 20% of the n being ≧2;
the groups R 1 are independently selected from:
(i) hydrogen; straight, branched or cyclic, saturated or unsaturated, n-valent hydrocarbon groups which have 1 to 30 carbon atoms, which optionally comprise one or more heteroatoms selected from oxygen, sulfur, nitrogen, and phosphorus within the carbon chains and/or at the end of the carbon chains thereof, and which are optionally substituted with one or more substituents selected from the group consisting of —OH, —COOH, —CN, —CHO), and ═O, and
(ii) n-valent radicals of biodegradable, biocompatible oligomers and polymers selected from the group consisting of polysaccharides, polypeptides, polyamides, polyesters, polycarbonates, polyethers, and fatty acid derivatives;
m is an integer from 0 to 4; and
the groups R 2 are selected from the group consisting of —OH, ═O, and
the options listed for R 1 ;
(b) 0 to 50% by weight of one or more a-olefin co-monomers;
(c) 0 to 10% by weight of one or more polymerization initiators selected from the group consisting of thermal initiators and photoinitiators; and
(d) 0 to 95% by weight of one or more solvents selected from the group consisting of water, lower alcohols, ether, ketone, ester, amide and hydrocarbon solvents;
shaping the composition; and
thermally or photochernically polymerizing and thus curing the shaped composition to provide the body implant.
2. The method according to claim 1 , wherein the vinyl ester monomer of the general formula (II) accounts for 50 mole percent of all monomers contained in the polymerization-curable composition.
3. The method according to claim 1 , wherein at least 35 mole percent of all vinyl ester monomers are difunctional or higher functional, cross-linking monomers in which n is ≧2.
4. The method according to claim 1 , wherein the a-olefin co-monomers used as the component (b) are selected from: (meth)acrylic acid, (meth)acrylic anhydride, (meth)acrylic acid glycidyl ester, (meth)acryloyloxy succinic acid anhydride, (meth)acryloyloxymethyl succinic anhydride, (meth)acrylic acid 2-oxo -1 ,3-dioxo lanylmethyl ester, vinyl succinic anhydride, vinylene carbonate, maleic acid, maleic anhydride, furmaric acid and vinylpyrrolidone.
5. The method according to claim 1 , wherein the polymerization-curable composition comprises, as a further component (e), one or more additives selected from the group consisting of polymerization sensitizers, polymerization inhibitors, stabilizers, modifying agents, softeners, dyeing agents, bioactive agents, cells, thickening agents, and fillers.
6. The method according to claim 5 , wherein the bioactive agents are selected from the group consisting of drugs, proteins, antibodies, and ligands.
7. The method according to claim 1 , wherein one or more additives are covalently bound to monomers or co-monomers.
8. The method according to claim 7 , wherein at least one additive covalently bound to monomers or co-monomers is a bioactive agent.
9. The method according to claim 1 , wherein part of the polymerization-curable composition is pre-cured, with which the remaining uncured composition is mixed, and the mixture is cured.
10. The method according to claim 1 , wherein the polymerization is carried out in the course of a generative manufacturing process.
11. The method according to claim 1 , wherein the shaped composition is subjected to one or more post-treatment step(s) after curing.
12. The method according to claim 11 , wherein the post-treatment steps are selected from the group consisting of post-curing, heat treatment, extraction, re-precipitation, and surface treatment steps.
13. The method according to claim 1 , wherein at least one vinyl ester monomer is selected from the group consisting of 1,4-butanediol bis(vinyl carbonate), 2-cyanoethyl vinyl carbonate, N,N′-dimethyl-1,2-ethylenediamine bis(vinyl carbamate), sarcosine methyl ester vinyl carbamate, N,O-bis(vinyloxycarbonyl)-N- methylhydroxylamine, N-methoxy vinyl carbamate, N-acryloyl-N-methoxy vinyl carbamate, vinyloxycarbonylphosphonic acid diethyl ester, 2-(diethoxyphosphoryloxy)ethylamine vinyl carbamate, ethyl bis[2-(vinyloxycarbonylamino)ethyl] phosphate, and divinyl ethyl phosphate.
14. The method according to claim 1 , wherein the shaping step is conducted in vivo.
15. The method according to claim 1 , wherein the shaping step is conducted in vivo while the composition is contained in a degradable container.
16. The method according to claim 1 , wherein the vinyl ester monomer of the general formula (II) accounts for 50 mole percent of all monomers contained in the polymerization-curable composition, and
at least 35 mole percent of all vinyl ester monomers are difunctional or higher functional, cross-linking monomers in which n is ≧2.