阅读说明：本技术 抗微生物接触镜 (Antimicrobial contact lenses ) 是由 伊齐耶·舒埃 于 2019-02-14 设计创作，主要内容包括：一种用于接触镜的抗微生物聚合物,包括至少一种抗微生物单体,和至少一种选自丙烯酸、疏水性丙烯酸、亲水性丙烯酸、乙烯基和胶原单体的其它单体。(An antimicrobial polymer for use in a contact lens comprising at least one antimicrobial monomer, and at least one other monomer selected from the group consisting of acrylic acid, hydrophobic acrylic acid, hydrophilic acrylic acid, vinyl, and collagen monomers.)

1. An antimicrobial polymer for use in contact lenses comprising

At least one antimicrobial monomer; and

at least one other monomer selected from: acrylic monomers, hydrophobic acrylic monomers, hydrophilic acrylic monomers, vinyl monomers, and/or collagen monomers.

2. The antimicrobial polymer of claim 1, wherein the at least one antimicrobial monomer is a quaternary ammonium salt-based monomer.

3. The antimicrobial polymer of claim 2, wherein the quaternary ammonium salt-based monomer is selected from the group consisting of: 1- [12- (methacryloyloxy) dodecyl ] pyridinium bromide (MDPB), methacryloyloxyethyl hexadecyldimethylammonium chloride (DMAE-CB), 2-methacryloyloxyethyl dodecyl methylammonium bromide (MAE-DB), 2-methacryloyloxyethyl hexadecylmethylammonium bromide (MAE-HB) and/or bis (2-methacryloyloxyethyl) dimethylammonium bromide (IDMA-1).

4. The antimicrobial polymer of claim 1, wherein the at least one antimicrobial monomer comprises a monomer having a primary, secondary, or tertiary amino group.

5. The antimicrobial polymer according to claim 4, wherein the at least one antimicrobial monomer is selected from the group consisting of o-, m-and/or p-dimethylaminomethylstyrene, N- (2-dimethylaminoethyl) acrylamide, N- (2-aminoethyl) acrylamide, N-butylacrylamide and/or diallyldimethylammonium salts.

6. The antimicrobial polymer of claim 1, wherein the at least one antimicrobial monomer is selected from dimethylaminopropyl methacrylate (DMAPM), dimethylaminohexyl methacrylate (DMAHM), dimethylaminoheptyl methacrylate (DMAHPM), dimethylaminooctyl methacrylate (DMAOM), dimethylaminonenyl methacrylate (DMANM), dimethylaminodecyl methacrylate (DMADM), dimethylaminoaundecyl methacrylate (DMAUDM), dimethylaminodecyl methacrylate (DMADDM), dimethylaminodecyl methacrylate (DMATDM), dimethylaminodecyl methacrylate (DMATTDM), dimethylaminopentadecyl methacrylate (DMAPDM), dimethylaminodecyl methacrylate (DMAHDM), dimethylaminodecyl heptadecyl methacrylate (DMAHPDM), Dimethylaminoctadecyl Methacrylate (DMAODM), dimethylaminocellobecyl methacrylate (DMANDM), dimethylaminocellosyl methacrylate (DMAIOM), dimethylaminocellosyl methacrylate (DMAHOM) and/or dimethylaminocellosyl methacrylate (DMADOM).

7. The antimicrobial polymer of claim 1, wherein the at least one antimicrobial monomer is covalently linked to an antimicrobial peptide.

8. The antimicrobial polymer of claim 5, wherein the at least one antimicrobial monomer is selected from the group consisting of: beta-sheet peptides (e.g., human alpha-and beta-defensins, fungal defensins, or porcine antimicrobial peptides) stabilized by 2-4 disulfide bonds, alpha-helical peptides (e.g., LL-37, cecropin, or magainin), extended structures rich in glycine, proline, tryptophan, arginine, or histidine (e.g., indolizidine), and/or cyclic peptides with one or more disulfide bonds (e.g., bacteriocins).

9. The antimicrobial polymer of claim 1, wherein the acrylic monomer is selected from the group consisting of: glycerol monomethacrylate, 2-hydroxyethyl methacrylate, N- (2-hydroxypropyl) methacrylamide, hydroxypropyl methacrylate, polyethylene glycol, monomethyl ether monomethacrylate, N-vinyl-2-pyrrolidone, isobutyl methacrylate, methyl methacrylate, N-octyl methacrylate, allyl phenyl ether, diphenylmethyl methacrylate, benzyl acrylate, N-benzyl methacrylamide, benzyl methacrylate, 2- (9H-carbazol-9-yl) ethyl methacrylate, 4-chlorophenyl acrylate, 1H, 7H-dodecafluoroheptyl methacrylate, 1H,2H, 2H-heptadecafluorodecyl acrylate, 1H,2H, 2H-heptadecafluorodecyl methacrylate, 1H-heptafluorobutyl acrylate, 1H, 3H-hexafluorobutyl methacrylate, hexafluoroisopropyl methacrylate, 1H, 5H-octafluoropentyl acrylate, 1H, 5H-octafluoropentyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentafluorophenyl acrylate, pentafluorophenyl methacrylate, 1H, 3H-tetrafluoropropyl methacrylate, 2,4, 6-tribromophenyl acrylate, 2,2, 2-trifluoroethyl methacrylate, N- (3-aminopropyl) methacrylamide monohydrochloride salt, 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-cinnamoyloxy-ethyl acrylate, cinnamyl methacrylate, glycidyl cinnamate, 2-naphthyl methacrylate, ethylene glycol dimethacrylate and/or 1, 4-phenylene diacrylate and polyethylene glycol diacrylate.

10. The antimicrobial polymer of claim 1, wherein the acrylic acid monomer is selected from the group consisting of methyl acrylate and methyl methacrylate.

11. The antimicrobial polymer of claim 1, wherein the hydrophobic acrylic monomer is selected from the group consisting of:

monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, crosslinked with the butanediol diacrylate;

monomers of ethyl acrylate, ethyl methacrylate and 2,2, 2-trifluoroethyl methacrylate are crosslinked with ethylene glycol dimethacrylate to form a copolymer of ethyl acrylate, ethyl methacrylate and 2,2, 2-trifluoroethyl methacrylate, and the copolymer is crosslinked with ethylene glycol dimethacrylate;

monomers of phenylethyl methacrylate, n-butyl acrylate and fluoroalkyl methacrylate which form a crosslinked copolymer of phenylethyl methacrylate, n-butyl acrylate and fluoroalkyl methacrylate;

monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, crosslinked with the butanediol diacrylate;

monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate which form copolymers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, and/or

Monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, which form a copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate.

12. The antimicrobial polymer of claim 1, wherein the hydrophilic acrylic monomer is selected from the group consisting of:

monomers of hydroxyethyl methacrylate and methyl methacrylate which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate;

monomers of hydroxyethyl methacrylate and methyl methacrylate which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate;

monomers of hydroxyethyl methacrylate and methyl methacrylate which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate;

monomers of 2-hydroxyethyl methacrylate and 2-ethoxyethyl methacrylate which form copolymers of 2-hydroxyethyl methacrylate and 2-ethoxyethyl methacrylate, and/or

Monomers of 2-hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of 2-hydroxyethyl methacrylate and methyl methacrylate.

13. The antimicrobial polymer of claim 1, wherein the vinyl monomer is selected from the group consisting of: vinyl carbonate, vinyl carbamate, N-vinyl-2-pyrrolidone and/or N-vinylcarbazole.

14. An antimicrobial polymer according to claim 1, wherein the collagen monomer is selected from: natural type I-XXVIII collagen monomers, recombinant collagen monomers and fragments thereof, and/or synthetic collagen monomers and fragments thereof.

15. The antimicrobial polymer of claim 1, wherein the antimicrobial polymer is transparent.

16. A method of making an antimicrobial polymer for a contact lens comprising:

reacting at least one antimicrobial monomer with at least one other monomer selected from acrylic monomers, vinyl monomers, and/or collagen monomers to obtain an antimicrobial polymer; and

the antimicrobial polymer is used in a contact lens.

17. The method of claim 15, wherein the at least one antimicrobial monomer is a quaternary ammonium salt-type monomer.

18. The method of claim 16, wherein the quaternary ammonium salt-based monomer is selected from the group consisting of: 1- [12- (methacryloyloxy) dodecyl ] pyridinium bromide (MDPB), methacryloyloxyethyl hexadecyldimethylammonium chloride (DMAE-CB), 2-methacryloyloxyethyl dodecyl methylammonium bromide (MAE-DB), 2-methacryloyloxyethyl hexadecylmethylammonium bromide (MAE-HB) and/or bis (2-methacryloyloxyethyl) dimethylammonium bromide (IDMA-1).

19. The method of claim 15, wherein the at least one antimicrobial monomer comprises a monomer having a primary, secondary, or tertiary amino group.

20. The method of claim 18, wherein the at least one antimicrobial monomer is selected from o-, m-, and/or p-dimethylaminomethylstyrene, N- (2-dimethylaminoethyl) acrylamide, N- (2-aminoethyl) acrylamide, N-butylacrylamide, and/or diallyldimethylammonium salts.

21. The method of claim 15, wherein the at least one antimicrobial monomer is selected from dimethylaminopropyl methacrylate (DMAPM), dimethylaminohexyl methacrylate (DMAHM), dimethylaminoheptyl methacrylate (DMAHPM), dimethylaminooctyl methacrylate (DMAOM), dimethylaminonenyl methacrylate (DMANM), dimethylaminodecyl methacrylate (DMADM), dimethylaminoaundecyl methacrylate (DMAUDM), dimethylaminoadodecyl methacrylate (DMADDM), dimethylaminoatridecyl methacrylate (DMATDM), dimethylaminodetradecyl methacrylate (DMATTDM), dimethylaminopentadecyl methacrylate (DMAPDM), dimethylaminocetyl methacrylate (DMAHDM), dimethylaminoceptadecyl methacrylate (DMAHPDM), Dimethylaminoctadecyl Methacrylate (DMAODM), dimethylaminocellobecyl methacrylate (DMANDM), dimethylaminocellosyl methacrylate (DMAIOM), dimethylaminocellosyl methacrylate (DMAHOM) and/or dimethylaminocellosyl methacrylate (DMADOM).

22. The method of claim 15, wherein the at least one antimicrobial monomer is covalently linked to an antimicrobial peptide.

23. The method of claim 21, wherein the at least one antimicrobial monomer is selected from the group consisting of: beta-sheet peptides (e.g., human alpha-and beta-defensins, fungal defensins, or porcine antimicrobial peptides) stabilized by 2-4 disulfide bonds, alpha-helical peptides (e.g., LL-37, cecropin, or magainin), extended structures rich in glycine, proline, tryptophan, arginine, or histidine (e.g., indolizidine), and/or cyclic peptides with one or more disulfide bonds (e.g., bacteriocins).

24. The method of claim 15, wherein the acrylic monomer is selected from the group consisting of: glycerol monomethacrylate, 2-hydroxyethyl methacrylate, N- (2-hydroxypropyl) methacrylamide, hydroxypropyl methacrylate, polyethylene glycol, monomethyl ether monomethacrylate, N-vinyl-2-pyrrolidone, isobutyl methacrylate, methyl methacrylate, N-octyl methacrylate, allyl phenyl ether, diphenylmethyl methacrylate, benzyl acrylate, N-benzyl methacrylamide, benzyl methacrylate, 2- (9H-carbazol-9-yl) ethyl methacrylate, 4-chlorophenyl acrylate, 1H, 7H-dodecafluoroheptyl methacrylate, 1H,2H, 2H-heptadecafluorodecyl acrylate, 1H,2H, 2H-heptadecafluorodecyl methacrylate, 1H-heptafluorobutyl acrylate, 1H, 3H-hexafluorobutyl methacrylate, hexafluoroisopropyl methacrylate, 1H, 5H-octafluoropentyl acrylate, 1H, 5H-octafluoropentyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentafluorophenyl acrylate, pentafluorophenyl methacrylate, 1H, 3H-tetrafluoropropyl methacrylate, 2,4, 6-tribromophenyl acrylate, 2,2, 2-trifluoroethyl methacrylate, N- (3-aminopropyl) methacrylamide monohydrochloride salt, 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-cinnamoyloxy-ethyl acrylate, cinnamyl methacrylate, glycidyl cinnamate, 2-naphthyl methacrylate, ethylene glycol dimethacrylate and/or 1, 4-phenylene diacrylate and polyethylene glycol diacrylate.

25. The method of claim 15, wherein the acrylic monomer is selected from the group consisting of methyl acrylate and methyl methacrylate.

26. The method of claim 15, wherein the hydrophobic acrylic monomer is selected from the group consisting of:

monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, crosslinked with the butanediol diacrylate;

monomers of ethyl acrylate, ethyl methacrylate and 2,2, 2-trifluoroethyl methacrylate are crosslinked with ethylene glycol dimethacrylate to form a copolymer of ethyl acrylate, ethyl methacrylate and 2,2, 2-trifluoroethyl methacrylate, and the copolymer is crosslinked with ethylene glycol dimethacrylate;

monomers of phenylethyl methacrylate, n-butyl acrylate and fluoroalkyl methacrylate which form a crosslinked copolymer of phenylethyl methacrylate, n-butyl acrylate and fluoroalkyl methacrylate;

monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, crosslinked with the butanediol diacrylate;

monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate which form copolymers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, and/or

Monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, which form a copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate.

27. The method of claim 15, wherein the hydrophilic acrylic monomer is selected from the group consisting of:

monomers of hydroxyethyl methacrylate and methyl methacrylate which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate;

monomers of hydroxyethyl methacrylate and methyl methacrylate which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate;

monomers of hydroxyethyl methacrylate and methyl methacrylate which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate;

monomers of 2-hydroxyethyl methacrylate and 2-ethoxyethyl methacrylate which form copolymers of 2-hydroxyethyl methacrylate and 2-ethoxyethyl methacrylate, and/or

Monomers of 2-hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of 2-hydroxyethyl methacrylate and methyl methacrylate.

28. The method of claim 15, wherein the vinyl monomer is selected from the group consisting of: vinyl carbonate, vinyl carbamate, N-vinyl-2-pyrrolidone and/or N-vinylcarbazole.

29. The method of claim 15, wherein the collagen monomer is selected from the group consisting of: natural type I-XXVIII collagen monomers, recombinant collagen monomers and fragments thereof, and/or synthetic collagen monomers and fragments thereof.

30. The method of claim 15, wherein the antimicrobial polymer is transparent.

31. The antimicrobial polymer of any one of claims 1-14, wherein the polymer comprises at least 20 atoms.

32. The antimicrobial polymer of any one of claims 1-14, wherein the polymer comprises at least 40 atoms.

33. The antimicrobial polymer of any one of claims 1-14 and 31-32, wherein the polymer is formed into a contact lens.

34. The antimicrobial polymer of any one of claims 1-14 and 31-32, wherein the polymer is formed into a contact lens and the monomer is non-leachable after completion of the contact lens manufacture.

35. The method of any one of claims 15-30, wherein the polymer comprises at least 20 atoms.

36. The method of any one of claims 15-30, wherein the polymer comprises at least 40 atoms.

37. The method of any one of claims 15-30 and 35-36, wherein the monomer is non-leachable after completion of the contact lens manufacture.

Technical Field

The present invention relates generally to contact lenses and methods of making and using the same, and more particularly to antimicrobial polymers for contact lenses obtained by copolymerizing at least one antimicrobial monomer with at least one other monomer.

Background

Contact lenses are lenses that "float" on the human tear film. They are not physically embedded in the body as implants do. The purpose of contact lenses is to refract light to properly focus the light on the retina and/or to change the cosmetic appearance of the eye.

Infection is a serious complication of contact lenses. Bacteria can adhere to the contact lens and spread to the ocular surface. Uncontrolled infection of the cornea due to the use of contact lenses can result in loss of vision and even eye loss.

The most common strategy for reducing the risk of infection is to use a contact lens storage solution with antimicrobial properties. Although this may be effective, it depends on whether the patient uses the correct contact lens solution. For cost reasons, patients will typically place contact lenses in saline without antimicrobial properties. Thus, there is a continuing risk of infection.

Another strategy proposed in the past has been to implant antimicrobial metal ions into the polymer of the contact lens. In particular, silver and copper metals have been proposed as agents for infusion into polymers for medical devices including contact lenses. Although the use of free metal ions in polymers as antimicrobial agents has been widely used in commercial plastics and some short-term disposable medical devices (e.g., catheters), metal ions are known to be harmful to the eye. Silver deposition (Argyrosis) is a medical term for silver toxicity in the eye. Silver deposits are reported to cause gray discoloration of the conjunctiva and iris. It has also been found that silver deposits can lead to cataracts and macular degeneration, both of which can threaten vision. Copper toxicity in the eye can lead to the appearance of a characteristic green ring around the cornea known as the Kayser-Fleischer ring. In addition, copper toxicity has been shown to induce ocular complications such as intraocular inflammation (uveitis), hemorrhage, vitreous liquefaction, low intraocular pressure, iris ischemia, and retinal damage. In addition, free metal ions may also leach out of the polymer over time, and thus, the polymer may lose its antimicrobial properties over time.

Dziabo et al have described quaternary ammonium-containing organosilanes for use in the manufacture of antimicrobial contact lenses. However, organosilanes present a number of difficulties in the manufacture of contact lenses. The quaternary ammonium-containing organosilanes can be used to make silicone-based contact lenses. However, the manufacture of silicone-based contact lenses requires very expensive equipment and often needs to be carried out at very low temperatures. The expense of the equipment and the particular manufacturing environment make silicone-based contact lenses available to only large companies. For most of the smaller contact lens manufacturers worldwide, the polymers used in contact lenses are mainly based on methacrylates. Other less common contact lens materials include vinyl and collagen. Most organosilane compounds do not polymerize into transparent materials in the presence of methacrylate, vinyl, or collagen and therefore cannot be used to make antimicrobial contact lenses based on methacrylate, vinyl, and/or collagen. Accordingly, there is a need for an invention that imparts antimicrobial properties to methacrylate, vinyl, and/or collagen-based contact lenses.

For the foregoing reasons, there remains a need in the art for improved compositions and methods for reducing the risk of microbial infection associated with contact lenses.

Disclosure of Invention

The present invention provides antimicrobial polymers for contact lenses obtained by copolymerizing at least one antimicrobial monomer with at least one other monomer selected from acrylic, vinyl and/or collagen monomers. The present invention also provides a method of making an antimicrobial polymer for use in a contact lens by reacting at least one antimicrobial monomer with at least one other monomer selected from acrylic acid, vinyl, and/or collagen monomers to obtain the antimicrobial polymer; and using the antimicrobial polymer in the contact lens.

The copolymers of the present invention are antimicrobial, biocompatible, and reversibly deformable, while also being transparent, translucent, or opaque. In a preferred aspect, the antimicrobial monomers of these copolymers are not leachable after contact lens manufacture is complete. Thus, the antimicrobial monomer is free floating and not toxic to the eye. These features are the best functions that are desired for the contact lens. Furthermore, because not only the surface of the copolymer, but the entire copolymer has antimicrobial properties, contact lenses made from such copolymers do not lose their antimicrobial properties even if the surface of the implant erodes over time. This is particularly important for contact lenses exposed to the surface of the eye, since blinking can lead to erosion of the polymer material. When the surface of the polymer of the present invention is eroded, the subsurface antimicrobial polymer can still kill microorganisms, thereby reducing the risk of infection for the patient.

Drawings

Fig. 1 shows a polymeric embodiment of an antimicrobial, transparent, biocompatible, reversibly deformable polymer.

Detailed Description

The following description is presented to enable any person skilled in the art to make and use the 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. "example" is used herein to mean "serving as an illustrative description". Any aspect or design described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other aspects or designs. Accordingly, the disclosure is not intended to be limited to the examples described and illustrated herein, but is intended to be consistent with the scope of the claims.

As used herein, any biopharmaceutical includes any fragment, modification or variant of a biologic, including any pegylated, glycosylated, lipidated, cyclized or conjugated form of a biologic or a fragment, modification or variant thereof or a prodrug of any of the foregoing. As used herein, any small molecule drug includes any salt, acid, base, hydrate, solvate, ester, isomer, or polymorph thereof or a metabolite or prodrug of any of the foregoing. The abbreviations used herein have their conventional meaning in the chemical and biological arts.

It should be understood that the specific order or hierarchy of steps in the methods disclosed herein are examples of exemplary approaches. It should be understood that the particular order or hierarchy of steps in the methods may be rearranged based on design preferences, while remaining within the scope of the present disclosure. Any accompanying method claims present steps in a sample order, and are not intended to be limited to the specific order or hierarchy presented.

The present disclosure provides antimicrobial polymers for contact lenses obtained by copolymerizing at least one antimicrobial monomer with at least one other monomer selected from acrylic acid, vinyl, and collagen monomers. The resulting antimicrobial polymer provides antimicrobial, biocompatible, which is also transparent, translucent, or opaque. These features are the best functions that are desired for the contact lens. Furthermore, not only the surface of the copolymer, but the entire copolymer has antimicrobial properties.

Important characteristics of antimicrobial polymers are the non-leachability of the antimicrobial monomers and their immobilization within the polymer after manufacture is complete. Antimicrobial monomers have been found to be toxic when exposed to animals in the free state. Smaller antimicrobial molecules are more likely to diffuse freely and may not be permanently immobilized on the polymer after polymerization. Thus, in a preferred aspect, the antimicrobial monomers of the present invention should contain at least 20 atoms, and preferably more than 40 atoms, per molecule.

In a preferred aspect, the antimicrobial polymer kills the contacted microorganisms by disrupting the microbial cells. For example, the antimicrobial polymers of the present invention are generally positively charged and can readily adsorb onto negatively charged surfaces of bacterial cell walls. Once adsorbed, the antimicrobial polymer chains diffuse through the cell wall, binding to and disrupting the cell membrane. Disruption of the cell membrane and subsequent leakage of cytoplasmic components can cause the bacteria to die in a process known as lysis.

Most bacterial cell walls are negatively charged, and therefore most antimicrobial polymers are positively charged to facilitate the adsorption process. However, this also readily produces negatively charged antimicrobial polymers that may be suitable for killing positively charged bacterial cells.

Fig. 1 shows a polymeric embodiment of an antimicrobial, transparent, biocompatible, reversibly deformable polymer. In this figure, the antimicrobial polymer is obtained by copolymerizing at least one antimicrobial monomer with at least one other monomer selected from acrylic acid, vinyl, and/or collagen monomers. After polymerization, the resulting polymer network includes immobilized antimicrobial polymers spaced throughout the network.

In one embodiment, the antimicrobial monomer is selected from quaternary ammonium salt monomers. A non-limiting example of a quaternary ammonium salt monomer is 1- [12- (methacryloyloxy) dodecyl ] pyridinium bromide (MDPB).

CH₂＝C(CH₃)C(O)O(CH₂)₁₂N⁺(C₅H₅)Br^-

MDPB

MDPB has been used as an antimicrobial monomer to reduce the risk of dental caries when copolymerized with dental adhesives and dental resins.

In other embodiments, at least one antimicrobial monomer is a quaternary ammonium salt monomer, such as methacryloyloxyethyl hexadecyldimethyl ammonium chloride (DMAE-CB).

CH₂＝C(CH₃)C(O)O(CH₂)₂N⁺(CH₃)₂(CH₂)₁₅CH₃Cl^-

DMAE-CB

It is also possible to increase the amount of antimicrobial monomer that can be incorporated into the polymeric material and subsequently enhance the antimicrobial activity by modifying the quaternary ammonium salt-based monomer to have two polymerizable methacrylic acid moieties.

Thus, in other embodiments, at least one antimicrobial monomer is a quaternary ammonium salt monomer, such as 2-methacryloyloxyethyl dodecyl methyl ammonium bromide (MAE-DB).

CH₂＝C(CH₃)C(O)O(CH₂)₂N⁺(CH₃)(CH₂)₂O(O)CC(CH₃)＝CH₂(CH₂)₁₂CH₃Br^-

MAE-DB

In other embodiments, at least one antimicrobial monomer is a quaternary ammonium salt monomer, such as 2-methacryloyloxyethyl hexadecylmethyl ammonium bromide (MAE-HB).

CH₂＝C(CH₃)C(O)O(CH₂)₂N⁺(CH₃)(CH₂)₂O(O)CC(CH₃)＝CH₂(CH₂)₁₆CH₃Br^-

MAE-HB

In other embodiments, at least one antimicrobial monomer is a quaternary ammonium salt monomer, such as bis (2-methacryloyloxyethyl) dimethylammonium bromide (IDMA-1).

CH₂＝C(CH₃)C(O)O(CH₂)₂N⁺(CH₃)₂(CH₂)₂O(O)CC(CH₃)＝CH₂Br^-

IDMA-1

In other embodiments, the at least one antimicrobial monomer may differ based on alkyl chain length. Examples of these include, but are not limited to, dimethylaminopropyl methacrylate (DMAPM), dimethylaminohexyl methacrylate (DMAHM), dimethylaminoheptyl methacrylate (DMAHPM), dimethylaminooctyl methacrylate (DMAOM), dimethylaminonenyl methacrylate (DMANM), dimethylaminodecyl methacrylate (DMADM), dimethylaminoaundecyl methacrylate (DMAUDM), dimethylaminoadodecyl methacrylate (DMADDM), dimethylaminoatridecyl methacrylate (DMATDM), dimethylaminoatetradecyl methacrylate (DMATTDM), dimethylaminopentadecyl methacrylate (DMAPDM), dimethylaminoacetyl methacrylate (DMAHDM), dimethylaminoaheptadecyl methacrylate (DMAHPDM), dimethylaminoaoctadecyl methacrylate (DMAODM), Dimethylaminoannodecyl Methacrylate (DMANDM), dimethylaminoaicosyl methacrylate (DMAIOM), dimethylaminoaheneicosyl methacrylate (DMAHOM), dimethylaminoaicosyl methacrylate (DMADOM), and/or combinations thereof.

In other embodiments, the antimicrobial monomer may have a primary, secondary, or tertiary amino group. Examples of these types of antimicrobial monomers include, but are not limited to, o-, m-, and/or p-dimethylaminomethylstyrene, N- (2-dimethylaminoethyl) acrylamide, N- (2-aminoethyl) acrylamide, N-butylacrylamide, and diallyldimethylammonium salts.

In another embodiment, the cytostatic monomer is covalently linked to a cytostatic peptide. Examples of cytostatic peptides include, but are not limited to: beta-sheet peptides stabilized by 2-4 disulfide bonds (e.g., human alpha-and beta-defensins, fungal defensins (plectasin), or porcine antimicrobial peptides (protegrin)); alpha-helical peptides (e.g., LL-37, cecropins, or magainins); an extension structure rich in glycine, proline, tryptophan, arginine or histidine (e.g., indolicidin); cyclic peptides with one or two disulfide bonds (e.g. bacteriocins).

In one embodiment, the at least one other monomer is selected from acrylic acid, vinyl and/or collagen monomers. These monomers can be polymerized with at least one antimicrobial monomer as described above to provide an antimicrobial polymer for use in contact lenses.

In other embodiments, suitable acrylic monomers for use in the manufacture of contact lenses include at least one of the following monomers: glycerol monomethacrylate, 2-hydroxyethyl methacrylate, N- (2-hydroxypropyl) methacrylamide, hydroxypropyl methacrylate, polyethylene glycol, monomethyl ether monomethacrylate, N-vinyl-2-pyrrolidone, isobutyl methacrylate, methyl methacrylate, N-octyl methacrylate, allyl phenyl ether, diphenylmethyl methacrylate, benzyl acrylate, N-benzyl methacrylamide, benzyl methacrylate, 2- (9H-carbazol-9-yl) ethyl methacrylate, 4-chlorophenyl acrylate, 1H, 7H-dodecafluoroheptyl methacrylate, 1H,2H, 2H-heptadecafluorodecyl acrylate, 1H,2H, 2H-heptadecafluorodecyl methacrylate, 1H-heptafluorobutyl acrylate, 1H, 3H-hexafluorobutyl methacrylate, hexafluoroisopropyl methacrylate, 1H, 5H-octafluoropentyl acrylate, 1H, 5H-octafluoropentyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentafluorophenyl acrylate, pentafluorophenyl methacrylate, 1H, 3H-tetrafluoropropyl methacrylate, 2,4, 6-tribromophenyl acrylate, 2,2, 2-trifluoroethyl methacrylate, N- (3-aminopropyl) methacrylamide monohydrochloride salt, 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-cinnamoyloxy-ethyl acrylate, cinnamyl methacrylate, glycidyl cinnamate, 2-naphthyl methacrylate, ethylene glycol dimethacrylate and/or 1, 4-phenylene diacrylate and polyethylene glycol diacrylate.

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

monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, crosslinked with butanediol diacrylate: (IQ) available from Erkon (Alcon), 6201, a division of Norwalk, Nvyc, Wasteburg, TX 76134-;

monomers of ethyl acrylate, ethyl methacrylate, 2,2, 2-trifluoroethyl methacrylate, crosslinked with ethylene glycol dimethacrylate, which form a copolymer of ethyl acrylate, ethyl methacrylate and 2,2, 2-trifluoroethyl methacrylate, crosslinked with ethylene glycol dimethacrylate ((AMO)) available from qiangsheng vision health, saint andelu P1 street 1700, CA 92705;

monomers of phenylethyl methacrylate, n-butyl acrylate and fluoroalkyl methacrylate which form crosslinked copolymers of phenylethyl methacrylate, n-butyl acrylate and fluoroalkyl methacrylate: (

(HOYA)), available from Haoya corporation, Tokyo Dou Xinjiang, Japan, No. 7,5, 2 Dies;

monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate, which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, crosslinked with butanediol diacrylate (HI56), available from

Company, axekoshima, savorenshil hill kanton, inc, CB 113 AU;

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 the company of research and development on gallop, sarasota, park, dawn 6447, FL 34243; and

monomers of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, which form a copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate (Benz HF-2), are available from the company of research and development on the gallows, pakland avenue No. 6447, FL 34243, sarasota.

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

monomers of hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate (CI26), available fromCompany, axekoshima, savorenshil hill kanton, inc, CB 113 AU;

monomers of hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate (MICS22), available fromCompany, IxoshireSavorenshil hill kanton mansion, saffreund, CB 113 AU;

monomers of hydroxyethyl methacrylate and methyl methacrylate, which form a copolymer of hydroxyethyl methacrylate and methyl methacrylate (CI18), available fromCompany, axekoshima, savorenshil hill kanton, inc, CB 113 AU;

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 and development, Inc., Parkland Dairy No. 6447, Salasota, FL 34243; and

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, Spakarta, Pakland Dairy 6447, FL 34243.

In other embodiments, the vinyl monomers used to make contact lenses include at least one of the following monomers: n-vinyl-2-pyrrolidone and/or N-vinylcarbazole. Non-limiting examples of vinyl monomers include, but are not limited to, vinyl esters (acrylates), vinyl carbonates (roc (o) OCH ═ CH₂) And vinyl carbamate (R' R "nc (o) OCH ═ CH₂). The vinyl monomer can be polymerized with the at least one antimicrobial monomer described above to provide an antimicrobial polymer for use in contact lenses.

In other embodiments, the collagen monomers used to make transparent, opaque or translucent, biocompatible contact lenses include at least one of the following monomers: natural type I-XXVIII collagen monomers, recombinant collagen monomers and fragments thereof, and/or synthetic collagen monomers and fragments thereof.

In one embodiment, the at least one other monomer is a collagen monomer. A single collagen molecule (tropocollagen) is used to compose larger collagen aggregates, such as fibrils. The fibril is composed of three polypeptide chains, each of which is identified as having a left-handed helix. The three left-handed helices are twisted into right-handed triple helices or microfibers, a mating quaternary structure stabilized by hydrogen bonds. Each microfiber is then interdigitated with its adjacent microfibers. In addition, the collagen monomer may be linked to one or more acrylate or vinyl monomers using a variety of linkers. The collagen monomer may also be polymerized with at least one antimicrobial monomer as described above to provide an antimicrobial polymer for use in contact lenses. In one embodiment, a contact lens may comprise collagen and N-isopropylacrylamide, collagen and 1-ethyl-3, 3' (dimethyl-aminopropyl) -carbodiimide, and collagen and N-hydroxysuccinimide (EDC/NHS).

While the features of the present invention have been particularly shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that the foregoing and other changes may be made therein without departing from the spirit and scope of the invention. Likewise, various figures may depict example architectures or other configurations for the present disclosure to aid in understanding features and functionality that may be included in the present disclosure. The present disclosure is not limited to the example architectures or configurations shown, but may be implemented using a variety of alternative architectures and configurations. In addition, while the present disclosure has been described above in terms of various exemplary embodiments and implementations, it should be understood that the applicability of the various features and functions described in one or more individual implementations is not limited to the particular implementation described above in which they are used. Rather, they may be applied, individually or in some combination, to one or more other embodiments of the disclosure, whether or not such embodiments are described, and whether or not such features are presented as being 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.

In the foregoing, the disclosure has been described with reference to specific exemplary embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the disclosure as set forth in the claims. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense. It is to be understood that the present disclosure is capable of use in various other combinations and embodiments and is capable of changes or modifications within the scope of the inventive concept as expressed herein.