Stock material or miscellaneous articles – Composite – Of epoxy ether
Reexamination Certificate
1995-11-17
2003-01-21
Tarazano, D. Lawrence (Department: 1773)
Stock material or miscellaneous articles
Composite
Of epoxy ether
C428S500000, C428S515000, C428S516000, C428S522000, C428S520000, C428S333000, C604S096010, C351S106000, C351S106000, C351S166000, C427S493000, C427S496000, C427S498000
Reexamination Certificate
active
06509098
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is generally in the area of the fabrication of poly(ethylene oxide) (“PEO”) coatings on surfaces.
PEO is a polymer which has many unique properties. It is soluble in a wide variety of solvents including water, benzene and tetrahydrofuran. In organic solvents, it solvates the monovalent metal ions, Li
+
, K
+
and Na
+
. PEO is unusual in its lack of interaction with biological matter and can provide an inert surface in certain biological applications. Merrill, E. W.,
J. Biomat. Sci. Polymer Edn.,
5:1-11 (1993). PEO is an important biomaterial because it is non-thrombogenic, i.e., it does not adsorb proteins of the intrinsic clotting system, and platelets do not adhere to it.
PEO star-shaped macromolecules are available which have many PEO chains or “arms” connected to a central body which is called the core. PEO star macromolecules can be synthesized, for example, by a living anionic polymerization using a divinylbenzene (DVB) core. Gnanou et al.,
Makromol. Chemie,
189:2885-2892 (1988); and Merrill,
J. Biomater. Sci. Polymer Edn.,
5:1-11 (1993).
There has been recent interest focused on the development of methods for coating surfaces with PEO. A PEO surface coating is very useful in blood-contacting devices, such as tubes and catheters, and products intended for diagnostic use, because such surfaces have the least non-specific binding to proteins and other biopolymers of any known synthetic polymer. Thus, the use of PEO coatings permits blood clotting to be minimized, and diagnostic assays to be improved.
A major problem has been the development of a thin, dense layers of PEO to cover support materials such as hard plastics, such as polyethylene terephthalate (“PETE”) or flexible materials, such as silicone rubber and segmented polyurethane.
U.S. Pat. Nos. 5,171,264 and 5,275,838 to Merrill disclose that a water solution of PEO, either linear or in star form, can be cross-linked by electron irradiation to form a hydrogel layer. The hydrogel has a thickness ranging down to about 0.5 mm, which is not strongly attached to the supporting material and rather easily sheared off. Upon attachment of affinity ligands to the hydrogels, the surfaces can be used for separating and purifying therapeutic proteins.
Alternatively, PEO polymers can be attached to surfaces by hydroxyl group activation followed by chemical coupling. The terminal hydroxyl groups of the PEO molecule can chemically activated, for example, by tresyl chloride, and then attached to a surface which contains appropriate reactive groups, e.g., amino or thiol. U.S. Pat. Nos. 5,171,264 and 5,275,838 to Merrill. There are, however, problems associated with this route. It is difficult to prepare stable surfaces having amino or thiol groups, and some procedures result in degradation of the surface to the extent that it can be readily washed off, thus providing no anchor for the PEO. Additionally, it is very difficult to implant linear PEO molecules on surfaces via this route with sufficient density to prevent the adsorption of biopolymers.
There is a need for methods for improving the hydrophilicity of hydrophobic polymer surfaces, while still maintaining the physical properties of the hydrophobic polymers. There is further a need for the development of methods for forming biocompatible coatings on surfaces. There further is a need for methods for producing hydrophilic coatings on surfaces to improve the biocompatibility of the surfaces, wherein the coatings can be readily derivatized by the attachment of biological molecules to the coating.
It is therefore an object of the invention to provide methods for the production of hydrophilic coatings on hydrophobic polymers. It is a further object of the invention to provide hydrophilic coatings on surfaces, such as PEO coatings, which reduce non-specific binding to the surfaces. It is still another object of the invention to provide methods for fabricating coatings on surfaces which can be readily derivatized by the attachment of biological molecules for use in a variety of biomedical applications.
SUMMARY OF THE INVENTION
Methods are provided for the fabrication of hydrophilic coatings on hydrophobic surfaces. In one embodiment, a poly(ethylene oxide) (“PEO”) coating is fabricated on the surface of a hydrophobic polymeric material by contacting the surface with a monomer comprising an unsaturated group, such as methacrylic acid or acrylic acid. The monomer then is reacted, for example by irradiation with an electron beam, to polymerize and, as a polymer, to be covalently attached to the surface. A coating of PEO molecules then may be attached to the polymer surface by hydrogen bond complexation. The PEO coating optionally may be covalently grafted onto the surface, for example, by irradiation grafting with an electron beam. The covalent polymerization and grafting of a coating of the monomers to the surface greatly improves the wettability of the surface, and also facilitates the covalent or non-covalent attachment of a coating of PEO to the hydrophobic polymer surface. Thus, hydrophilic PEO coatings can be fabricated on hydrophobic polymer surfaces, to improve the biocompatibility and other properties of the polymers, and to provide coated polymers which can be used in a variety of different applications.
DETAILED DESCRIPTION OF THE INVENTION
Methods for the fabrication of hydrophilic coatings on hydrophobic surfaces are provided. In one embodiment, a monomer comprising an unsaturated group is grafted onto the surface, for example, by irradiation with an electron beam, to produce a polymer surface with improved wettability properties. A poly(ethylene oxide) coating then is attached to the treated surface by hydrogen bond complexation. The poly(ethylene oxide) coating then optionally may be covalently grafted onto the surface, for example, by electron beam irradiation. The poly(ethylene oxide) coatings improve the biocompatibility and hydrophilicity of the polymer surface. The surfaces may be further reacted, for example, by the attachment of a biologically active molecule, such as protein, to the surface. The polymer surfaces thus may be derivatized for use in a wide variety of biomedical applications.
Glossary of Terms
The following abbreviations are defined so that their use in this application is unambiguous:
TABLE 1
Definition of Abbreviations
Abbreviation
Definition
MA
methacrylic acid (monomer)
PMA
poly(methacrylic acid)
AA
acrylic acid (monomer)
PAA
poly(acrylic acid)
NVP
n-vinyl pyrrolidone (monomer)
PVP
poly(n-vinyl pyrrolidone)
HEMA
hydroxyethyl methacrylate (monomer)
PHEMA
poly(hydroxethyl methacrylate)
PVC
poly(vinyl chloride)
PVCAC
poly(vinyl chloride-co-vinyl acetate)
PES
poly(ether sulfone)
PS
polystyrene
PMMA
poly(methyl methacrylate)
PE
polyethylene
PE-UHMW
polyethylene, ultrahigh molecular weight
LDPE
low density polyethylene
PEG
poly(ethylene glycol)
PEO
linear poly(ethylene oxide)
STAR PEO
multi-armed molecule, with a central core and
multiple PEO chains extending from the central
core, wherein the PEO chains have hydroxyl
temini
SPU
segmented polyurethane or poly(urethane-urea)
PDMS
poly(dimethyl siloxane)
PVd
2
F
2
poly(vinylidene fluoride)
Monomers
Monomers comprising an unsaturated group, such as methacrylic acid or acrylic acid, can be grafted onto hydrophobic polymer surfaces to improve the hydrophilicity of the surfaces. Grafting of the monomers to the hydrophobic surfaces greatly improves the wettability properties of the surfaces, and permits the attachment of other polymers to the surfaces, to further improve the hydrophilicity, or other properties of the polymer surfaces. In one embodiment, the monomer is attached to the surface by irradiating the monomer on the surface with an electron beam, to cause polymerization and covalent attachment of the polymerized monomer on the surface as coating.
Monomers comprising an unsaturated group available in the art can be used which are capable of reacting with a hydrophobic polymer surface, to enhance the hydrophilicity of the surface, fo
Allgor Susan S.
Leung Gladys C.
Merrill Edward W.
Holland & Knight LLP
Massachusetts Institute of Technology
Tarazano D. Lawrence
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