Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
2003-05-13
2004-04-20
Zalukaeva, Tatyana (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Polymers from only ethylenic monomers or processes of...
C526S307100, C526S305000, C526S307600, C526S313000, C526S318100, C526S317100, C526S319000, C526S320000, C526S321000, C526S323100, C623S006110
Reexamination Certificate
active
06723815
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 at least 5 to about 90% water and comprises
(i) a hydrophobic aryl acrylic monomer of formula (I)
wherein:
A is H, CH
3
, CH
2
CH
3
, or CH
2
OH;
B is (CH
2
)
m
or [O(CH
2
)
2
]
n
;
C is (CH
2
)
w
;
m is 2-6;
n is 1-10;
Y is nothing, 0, S, or NR, provided that if Y is O, S, or NR, then B is (CH
2
)
m
;
R is H, CH
3
, CnH
2n+1
(n=1-10), iso-OC
3
H
7
, C
6
H
5
, or CH
2
C
6
H
5
;
w is 0-6, provided that m+w<8; and
D is H, C
1
-C
4
alkyl, C
1
-C
4
alkoxy, C
6
H
5
, CH
2
C
6
H
5
or halogen;
(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates; n-vinyl pyrrolidone 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) a hydrophobic aryl acrylic monomer of formula (I);
(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates; n-vinyl pyrrolidone 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.
Preferred aryl acrylic monomers of formula (I) for use in the coating materials of the present invention are those wherein A is CH
3
, B is (CH
2
)
m
, m is 2-5, Y is nothing or O, w is 0-1, and D is H. Most preferred monomers of formula (I) are 2-phenylethyl methacrylate (“2-PEMA”); 3-phenylpropyl methacrylate; 4-phenylbutyl methacrylate; 5-phenylpentyl methacrylate; 2-benzyloxyethyl methacrylate; and 3-benzyloxypropyl methacrylate.
Monomers of structure I are known and can be made by known methods. For example, the conjugate alcohol of the desired monomer can be combined in a reaction vessel with methyl methacrylate, tetrabutyl titanate (catalyst), and a polymerization inhibitor such as 4-benzyloxy phenol. The vessel can then be heated to facilitate the reaction and distill off the reaction by-products to drive the reaction to completion. Alternative synthesis schemes involve adding methacrylic acid to the conjugate alcohol and catalyzing with a carbodiimide or mixing the conjugate alcohol with methacryloyl chloride and a base such as pyridine or triethylamine.
The coating material contains an aryl acrylic monomer of formula (I) in an amount generally ranging from 10-60%, and preferably ranging from 20-50%.
The coating material contains an amount of hydrophilic monomer (separate from the reactive plasticizer ingredient described below) generally ranging from 5-70%. Suitable acrylamides include methacrylamide, ethacrylamide and propacrylamide as well as alkyl and aryl substituted acrylamides, such as dimethyl (meth)acrylamide; diethyl (meth)acrylamide and dipropyl (meth)acrylamide. The most preferred acrylamides are dimethyl methacrylamide and dimethyl acrylamide. Preferred hydrophilic monomers for use in the coating material are hydroxyalkyl (meth)acrylates and n-vinyl pyrrolidone (“NVP”). 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; NVP and mixtures thereof. The most preferred mixture of hydrophilic monomers is a combination of GMMA and n-vinyl pyrrolidone.
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 at least 5 to about 90% water, and preferably from about 30 to about 80% water. The proportion of the copolymer's monomers will depend on the desired water content. In a most preferred embodiment, the desired water content is about 40 to about 60% and the coating material comprises from 20 to 50% of a monomer of formula (I), from 5 to 20% of GMMA, from 0 to 40% of NVP, 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,
Callaghan Thomas A.
Leboeuf Albert R.
Alcon Inc.
Ryan Patrick M.
Zalukaeva Tatyana
LandOfFree
Covalently-bound, hydrophilic coating compositions for... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Covalently-bound, hydrophilic coating compositions for..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Covalently-bound, hydrophilic coating compositions for... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3195097