Covalently-bound, hydrophilic coating compositions for...

Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...

Reexamination Certificate

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C526S307100, C526S305000, C526S307600, C526S313000, C526S318100, C526S317100, C526S319000, C526S320000, C526S321000, C526S323100, C427S002240, C427S162000, C427S164000, C427S284000, C623S006110

Reexamination Certificate

active

06632905

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to coatings for surgical implants. In particular, the present invention relates to hydrophilic, covalently cross-linked copolymers that are covalently bound to the surface of surgical implants.
BACKGROUND OF THE INVENTION
Both rigid and foldable implantable ophthalmic lens materials are known. The most common rigid material used in ophthalmic implants is polymethyl methacrylate (“PMMA”). Foldable intraocular lens (“IOL”) materials can generally be divided into three categories: silicone materials, hydrogel materials, and non-hydrogel (“hydrophobic”) acrylic materials. See, for example,
Foldable Intraocular Lenses
, Ed. Martin et al., Slack Incorporated, Thorofare, N.J. (1993). For purposes of the present application, hydrophobic acrylic materials are acrylic materials that absorb less than approximately 5% water at room temperature.
Silicone and non-hydrogel acrylic materials used in ophthalmic implants can potentially damage endothelial cells and perhaps other cells or tissues as well during or after the implant's insertion in the eye. These materials are generally hydrophobic and/or tacky and can pull cells off of eye tissues that contact the implant. Particularly in the case of phakic IOL's implanted between the capsular bag and the iris, there is significant potential for physical contact between the implant and surrounding cells or tissue even after the implant reaches its target location.
SUMMARY OF THE INVENTION
The present invention relates to hydrophilic coating compositions for surgical implants, particularly ophthalmic implants comprising silicone, hydrophobic acrylic or hydrogel materials. More specifically, the present invention relates to a copolymeric coating material for an implant where the copolymeric coating material is capable of absorbing from about 40 to about 70% water and comprises
(i) 2-phenylethyl (meth)acrylate;
(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates; and acrylamides; and
(iii) a reactive plasticizer selected from the group consisting of polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates.
The present invention also relates to methods for applying the copolymeric coating material as specified above to an implant's surface. In one embodiment, the method comprises dissolving the copolymer containing a latent cross-linking agent in a solvent to form a coating solution, contacting the coating solution with the implant's surface, and activating the latent cross-linking agent in the coating copolymer. In another embodiment, the method comprises dissolving the copolymer in a solvent to form a coating solution, adding a cross-linking agent to the coating solution, contacting the coating solution with the implant's surface, and heating the coated implant to generate cross-linking.
DETAILED DESCRIPTION OF THE INVENTION
Unless indicated otherwise, all amounts are expressed as weight %.
The coating material of the present invention is a copolymer comprising:
(i) 2-phenylethyl (meth)acrylate;
(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates; and acrylamides; and
(iii) a reactive plasticizer selected from the group consisting of polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates.
The coating material contains 2-phenyethyl (meth)acrylate in an amount generally ranging from 20-60%. The most preferred 2-phenylethyl (meth)acrylate is 2-phenylethyl methacrylate (“2-PEMA”).
The coating material contains an amount of hydrophilic monomer generally ranging from 20-40%. Preferred hydrophilic monomers are hydroxyalkyl (meth)acrylates. Most preferred are 2-hydroxyethyl methacrylate; 1,3-dihydroxypropyl methacrylate; 2,3-dihydroxypropyl methacrylate; mixtures of 1,3- and 2,3-dihydroxypropyl methacrylate (“GMMA”); monomethoxy glyceryl methacrylate; and mixtures thereof.
Suitable reactive plasticizers or softening agents include polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates. These ingredients can reduce or minimize haze or crazing. Methacrylates are preferred, with PEG(400)monomethylether monomethacrylate most preferred. The amount of the reactive plasticizer will range generally from about 20 to about 40%. Depending on the implant's function and the thickness of the coating, some degree of haze or crazing may be tolerated such that large amounts of the reactive plasticizer may not be required.
The coating material is capable of absorbing from about 40 to about 70% water, preferably from about 42 to about 55% water. The proportion of the copolymer's monomers will depend on the desired water content. In a preferred embodiment, the desired water content is about 42 to about 55% and the coating material is comprises from 25 to 40% of 2-PEMA, from 20 to 40% of GMMA, and from 20 to 40% of polyethylene glycol (400) monomethylether monomethacrylate.
In one embodiment, in addition to the ingredients described above, the coating material also comprises a latent cross-linking agent, such as a blocked isocyanate. Suitable blocked isocyanate compounds include imidazole blocked isocyanatoethyl methacrylate. In this embodiment, the latent cross-linking agent is copolymerized with the other ingredients of the coating copolymer. In an alternative embodiment, the cross-linking agent is not added until the point where the coating copolymer is dissolved to form a coating solution. Examples of cross-linking agents that are suitable for use in this alternative embodiment include di-imidazole blocked 1,12-isocyanatododecane and peroxides, such as benzoyl peroxide and 2,4-dichlorobenzoyl peroxide.
The amount of the cross-linking agent contained in the coating compositions of the present invention will depend upon, among other factors, the chosen cross-linking agent and the degree of cross-linking desired. In general, the amount of the cross-linking agent necessary to cross-link the coating composition and secure it to the implant's surface will be about 0.5-3% for blocked isocyanates and about 3-6% for peroxides.
The copolymeric coating material is prepared by combining the chosen 2-phenylethyl (meth)acrylate, hydrophilic monomer, reactive plasticizer, and a polymerization initiator (optionally with a latent cross-linking agent) to form a coating composition and then curing the coating composition. Any type of polymerization initiator may be used, including thermal initiators and photoinitiators, provided that the initiator can be activated without activating the latent cross-linking agent if present. Preferred initiators are UV- and blue-light activated initiators. The most preferred initiator is the benzoylphosphine oxide initiator, 2,4,6-trimethyl-benzoyidiphenylophosphine oxide (“TPO”), which is activated by blue-light. The amount of the polymerization initiator in the coating compositions of the present invention will depend upon the curing conditions. In general, however, the amount will be about 3% (w/w) or less, preferably about 2% (w/w) or less, and most preferably about 1% (w/w).
In order to prevent premature cross-linking, the coating compositions of the present invention do not contain significant amounts of monomers having more than one unsaturated bond. Such ingredients include the common cross-linking monomers ethyleneglycol dimethacrylate; diethylene glycol dimethacrylate; ethyleneglycol diacrylate; allyl methacrylates; allyl acrylates; 1,3-propanediol dimethacrylate; 1,6-hexanediol dimethacrylate; 1,4-butanediol dimethacrylate; polyethyleneoxide diacrylates; and the like.
In addition to the 2-phenylethyl (meth)acrylate, hydrophilic monomer, plasticizer, any latent cross-linking agent, and polymerization initiator, the coating compositions optionally include one or more ingredients selected from the group consisting of UV absorbers that are copolymerizable with the 2-phenylethyl (meth)acr

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