Cell growth inhibiting copolymer for use in ophthalmic implants

Abstract

A cell growth inhibiting polymer for use in an ophthalmic implant includes at least one cell growth inhibiting monomer; and at least one other monomer selected from an acrylic monomer, a hydrophobic acrylic monomer, a hydrophilic acrylic monomer, a silicone monomer, a vinyl monomer and/or a collagen monomer.

Claims

1. A cell growth inhibiting polymer for use in an ophthalmic implant, comprising: at least one cell growth inhibiting monomer; and at least one other monomer selected from monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate, which forms a copolymer of phenylethyl acrylate and phenylethyl methacrylate, cross linked with butanediol diacrylate; wherein the at least one cell growth inhibiting monomer is a quaternary ammonium-based salt monomer; and wherein the quaternary ammonium-based salt monomer is selected from methacryloyloxydodecylpyridium bromide (MDPB), methacryloxyethyl cetyl ammonium chloride (DMAE-CB), 2-methacryloxyethyl dodecyl methyl ammonium bromide (MAE-DB), 2-methacryloxyethyl hexadecyl methyl ammonium bromide (MAE-HB), and/or bis(2-methacryloxyethyl) dimethyl ammonium bromide (IDMA-1).

2. The cell growth inhibiting polymer according to claim 1, wherein the cell growth inhibiting polymer is clear, opaque, or translucent.

3. The cell growth inhibiting polymer according to claim 1, wherein the cell growth inhibiting polymer is reversibly deformable.

4. The cell growth inhibiting polymer according to claim 1, wherein the ophthalmic implant is an artificial cornea or a glaucoma valve.

5. An article of manufacture, comprising: an ophthalmic implant, the implant comprising a cell growth inhibiting polymer, the cell growth inhibiting polymer comprising: at least one cell growth inhibiting monomer; and at least one other monomer selected from monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate, which forms a copolymer of phenylethyl acrylate and phenylethyl methacrylate, cross linked with butanediol diacrylate; wherein the at least one cell growth inhibiting monomer is a quaternary ammonium-based salt monomer; and wherein the quaternary ammonium-based salt monomer is selected from methacryloyloxydodecylpyridium bromide (MDPB), methacryloxyethyl cetyl ammonium chloride (DMAE-CB), 2-methacryloxyethyl dodecyl methyl ammonium bromide (MAE-DB), 2-methacryloxyethyl hexadecyl methyl ammonium bromide (MAE-HB), and/or bis(2-methacryloxyethyl) dimethyl ammonium bromide (IDMA-1).

6. The article of manufacture according to claim 5, wherein the cell growth inhibiting polymer is clear, opaque, or translucent.

7. The article of manufacture according to claim 5, wherein the cell growth inhibiting polymer is reversibly deformable.

8. The article of manufacture according to claim 5, wherein the ophthalmic implant is an artificial cornea.

9. The article of manufacture according to claim 5, wherein the ophthalmic implant is a glaucoma valve.

Description

BRIEF DESCRIPTION OF THE DRAWING

(1) FIG. 1 illustrates an embodiment of the polymerization of a cell growth inhibiting, biocompatible, reversibly deformable polymer.

DETAILED DESCRIPTION OF THE EMBODIMENTS

(2) The following description is presented to enable a person of ordinary skill in the art to make and use embodiments described herein. Descriptions of specific devices, techniques, and applications are provided only as examples. Various modifications to the examples described herein will be readily apparent to those of ordinary skill in the art, and the general principles defined herein may be applied to other examples and applications without departing from the spirit and scope of the disclosure. The word “exemplary” is used herein to mean “serving as an example illustration.” Any aspect or design described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Thus, the present disclosure is not intended to be limited to the examples described herein and shown but is to be accorded the scope consistent with the claims.

(3) As used herein, reference to any biological drug includes any fragment, modification or variant of the biologic, including any pegylated form, glycosylated form, lipidated form, cyclized form or conjugated form of the biologic or such fragment, modification or variant or prodrug of any of the foregoing. As used herein, reference to any small molecule drug includes any salt, acid, base, hydrate, solvate, ester, isomer, or polymorph thereof or metabolite or prodrug of any of the foregoing. Abbreviations used herein have their conventional meaning within the chemical and biological arts.

(4) It should be understood that the specific order or hierarchy of steps in the process disclosed herein is an example of exemplary approaches. Based upon design preferences, it is understood that the specific order or hierarchy of steps in the processes may be rearranged while remaining within the scope of the present disclosure. Any accompanying method claims present elements of the various steps in a sample order and are not meant to be limited to the specific order or hierarchy presented.

(5) Accordingly, the present disclosure is directed to a cell growth inhibiting polymer obtained by copolymerizing at least one cell growth inhibiting monomer and at least one other monomer selected from an acrylic, silicone, vinyl and/or collagen monomers. The copolymer of the present disclosure is a cell growth inhibiting, biocompatible and reversibly deformable copolymer. Further, the copolymer according to the present disclosure can be used in ophthalmic implant devices. In other aspects, the disclosed copolymer material is a clear, opaque, or translucent material suitable for use in at least some applications.

(6) In one embodiment, the cell growth inhibiting monomer is selected from quaternary ammonium-based monomers. An example of a quaternary ammonium-based monomer is methacryloyloxy dodecyl pyridium bromide (MDPB). MDPB has been used to reduce the risk of dental caries when copolymerized with dental adhesives and dental resins. MDPB has also been shown to inhibit mammalian cellular growth. Another example of a quaternary ammonium-based monomer is the monomer methacryloxyethyl cetyl ammonium chloride (DMAE-CB).

(7) In another embodiment, it is also possible to increase the amount of cell growth inhibiting monomers that can be incorporated into polymeric materials and thereby enhance the cell growth inhibiting activity by modifying quaternary ammonium monomers to have two polymerizable methacrylic moieties.

(8) In another embodiment, the cell growth inhibiting monomer may have primary, secondary or tertiary amino groups. Examples of these types of cell growth inhibiting monomers include but are not limited to phenylene ethynylene, dimethylamino methyl styrene, octylstyrene, dimethylamino ethyl acrylamide, aminoethyl acrylamide, n-butylacrylamide and diallylammonium salts that contain either secondary or tertiary amino groups.

(9) In yet another embodiment, the cell growth inhibiting monomer is covalently linked to a cell growth inhibiting peptide. Examples of cell growth inhibiting peptides include: β-sheet peptides stabilized by two to four disulfide bridges (e.g., human α- and β-defensins, plectasin or protegrins), α-helical peptides (e.g., LL-37, cecropins or magainins), extended structures rich in glycine, proline, tryptophan, arginine or histidine (e.g., indolicidin), and loop peptides with one or disulfide bridge (e.g., bacteriocins).

(10) In other embodiments, suitable acrylic monomers used to create a biocompatible, reversibly deformable polymer include at least one of the following monomers: glycerol monomethacrylate, 2-hydroxyethyl methacrylate, N-(2-hydroxypropyl)methacrylamide, hydroxypropyl methacrylate, poly(ethyleneglycol), monomethylether monomethacrylate, N-vinyl-2-pyrrolidone, isobutyl methacrylate, methyl methacrylate, N-octyl methacrylate, allyl phenyl ether, benzhydryl methacrylate, benzyl acrylate, N-benzyl methacrylamide, benzyl methacrylate, 2-(9H-carbazol-9-yl)ethyl methacrylate, 4-chlorophenyl acrylate, 1H,1H,7H-dodecafluoroheptyl methacrylate, 1H,1H,2H,2H-heptadecafluorodecyl acrylate, 1H,1H,2H,2H-heptadecafluorodecyl methacrylate, 1H,1H-heptafluorobutyl acrylate, 1H,1H,3H-hexafluorobutyl acrylate, 1H,1H,3H-hexafluorobutyl methacrylate, hexafluoroisopropyl methacrylate, 1H,1H,5H-octafluoropentyl acrylate, 1H,1H,5H-octafluoropentyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentafluorophenyl acrylate, pentafluorophenyl methacrylate, 1H,1H,3H-tetrafluoropropyl methacrylate, 2,4,6-tribromophenyl acrylate, 2,2,2-trifluoroethyl acrylate, 2,2,2-trifluoroethyl methacrylate, N-(3-aminopropyl)methacrylamide mono hydrochloride, 2-(N,N-dimethylamino)monoethyl methacrylate, methacrylic acid, 2-aminoethyl methacrylate hydrochloride, 4-(2-acryloxyethoxy)2-hydroxybenzophenone, phenyl acrylate, 4-methacryloxy-2-hydroxybenzophenone, 2-(2′-methacryloxy-5′-methylphenyl)benzotriazole, 2-cinnamoyloxyethyl acrylate, cinnamyl methacrylate, glycidyl cinnamate, 2-naphthyl methacrylate, ethylene glycol dimethacrylate, 1,4-phenylene diacrylate, and poly(ethylene glycol) diacrylate.

(11) In an embodiment, the at least one other monomer is selected a hydrophobic acrylic monomer. Examples of hydrophobic acrylic monomers include but are not limited to:

(12) Monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate, which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, cross linked with butanediol diacrylate (AcrySof® IQ) available from Alcon, A Novartis Division, 6201 South Frees ray, Fort Worth, Tex. 76134-2001;

(13) Monomers of ethyl acrylate, ethyl methacrylate, 2,2,2-trifluoroethyl methacrylate, cross linked with ethylene glycol dimethacrylate, which form a copolymer of ethyl acrylate, ethyl methacrylate, 2,2,2-trifluoroethyl methacrylate, cross linked with ethylene glycol dimethacrylate (Tecnis® (AMO)) available from Johnson & Johnson Vision Surgical, 1700 E St Andrew Pl, Santa Ana, Calif. 92705;

(14) Monomers of phenylethyl methacrylate, n-butyl acrylate, and fluoroalkyl methacrylate, which form a cross linked copolymer of phenylethyl methacrylate, n-butyl acrylate, and fluoroalkyl methacrylate (AF-1® (HOYA)) available from Hoya Corporation, 7-5, Naka-Ochiai 2-chome, Shinjuku-ku Tokyo, Japan;

(15) Monomers of phenylethyl acrylate, phenylethyl methacrylate, and butanediol diacrylate, which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, cross-linked with butanediol diacrylate (HI56) available from Contamac® Ltd., Carlton House, Shire Hill, Saffron Walden, Essex CB11 3AU;

(16) Monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, which form a copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate (BENZ HF-1.2) available from Benz Research & Development Corporation, 6447 Parkland Drive, Sarasota, Fla. 34243; and

(17) Monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, which form a copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate (Benz HF-2) available from Benz Research & Development Corporation, 6447 Parkland Drive, Sarasota, Fla. 34243.

(18) In an embodiment, the at least one other monomer is selected a hydrophilic acrylic monomer. Examples of hydrophilic acrylic monomers include but are not limited to:

(19) Monomers of hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate (CI26) available from Contamac® Ltd., Carlton House, Shire Hill, Saffron Walden, Essex CB11 3AU;

(20) Monomers of hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate (MICS22) available from Contamac® Ltd., Carlton House, Shire Hill, Saffron Walden, Essex CB11 3AU;

(21) Monomers of hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate (CI18) available from Contamac® Ltd., Carlton House, Shire Hill, Saffron Walden, Essex CB11 3AU;

(22) Monomers of 2-hydroxyethyl methacrylate and 2-ethoxyethyl methacrylate, which form a copolymer of 2-hydroxyethyl methacrylate and 2-ethoxyethyl methacrylate (Benz IOL 125 available from Benz Research & Development Corporation, 6447 Parkland Drive, Sarasota, Fla. 34243; and

(23) Monomers of 2-hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of 2-hydroxyethyl methacrylate and methyl methacrylate (BenzFlex 26) available from Benz Research & Development Corporation, 6447 Parkland Drive, Sarasota, Fla. 34243.

(24) In other embodiments, the silicone monomers used to create a biocompatible, reversibly deformable polymer include at least one of the following monomers: dimethylsiloxane and/or dimethyldiphenylsiloxane monomers.

(25) In other embodiments, the vinyl monomers used to create a biocompatible, reversibly deformable polymer include at least one of the following monomers: N-vinyl-2-pyrrolidone and/or N-vinyl carbazole monomers.

(26) In other embodiments, the collagen monomers used to create a clear, opaque, or translucent, biocompatible, reversibly deformable polymer include at least one of the following monomers: naturally derived type I-XXVIII collagen monomers, recombinant collagen monomers and fragments thereof, and/or synthetic collagen monomers and fragments thereof.

(27) FIG. 1 illustrates an embodiment of the polymerization of a cellular growth inhibiting, reversibly deformable polymer. In this FIGURE, the cellular growth inhibiting polymers are obtained by copolymerizing at least one cellular growth inhibiting monomer with at least one monomer selected from an acrylic, silicone, vinyl and/or collagen monomer. After polymerization, the resulting polymeric network includes the immobilized cellular growth inhibiting polymer spaced throughout the network.

(28) While the inventive features have been particularly shown and described with reference to preferred embodiments thereof, it will be understood by those in the art that the foregoing and other changes may be made therein without departing from the sprit and the scope of the disclosure. Likewise, the various diagrams may depict an example architectural or other configuration for the disclosure, which is done to aid in understanding the features and functionality that can be included in the disclosure. The disclosure is not restricted to the illustrated example architectures or configurations but can be implemented using a variety of alternative architectures and configurations. Additionally, although the disclosure is described above in terms of various exemplary embodiments and implementations, it should be understood that the various features and functionality described in one or more of the individual embodiments are not limited in their applicability to the particular embodiment with which they are described. They instead can be applied alone or in some combination, to one or more of the other embodiments of the disclosure, whether or not such embodiments are described, and whether or not such features are presented as being a part of a described embodiment. Thus, the breadth and scope of the present disclosure should not be limited by any of the above-described exemplary embodiments.