HK1138217A - Processes to prepare antimicrobial contact lenses - Google Patents

Description

Method for making antimicrobial contact lenses

RELATED APPLICATIONS

This application is a non-provisional filing of U.S. provisional application serial No. 60/863,698 filed on 31/10/2006.

Technical Field

The present invention relates to a method of making an antimicrobial lens.

Background

Contact lenses have been used commercially for improving vision since 1950. The first contact lenses were made of hard materials. Used by the patient at a wake time and removed for cleaning. Developments in this area have now resulted in soft contact lenses that can be worn continuously for days or longer without the need for removal for cleaning. Although many patients prefer these lenses for their increased comfort, these lenses can cause certain adverse reactions to the user. Bacteria or other microorganisms, particularly Pseudomonas aeruginosa (Pseudomonas aeruginosa), can grow on the surface of soft contact lenses over time. The accumulation of bacteria and other microorganisms can cause adverse side effects such as acute red eye on contact lenses and the like. Although the problem of bacteria and other microorganisms is mostly associated with the long-term use of soft contact lenses, the accumulation of bacteria and other microorganisms also occurs in the wearer of hard contact lenses.

US5,820,918 discloses medical devices made of a water-absorbable polymeric material and a medical compound having low solubility in aqueous solutions, such as a preserved or radiopaque compound. However, the procedures disclosed in the embodiments result in opaque devices that are not suitable for use in ophthalmic devices (e.g., contact lenses).

Accordingly, there is a need to produce contact lenses that inhibit the growth of bacteria or other microorganisms and/or the adherence of bacteria or other microorganisms on the surface of the contact lenses. There is also a need to produce contact lenses that do not promote the adhesion and/or growth of bacteria or other microorganisms on the surface of the contact lenses. There is also a need to produce contact lenses that inhibit adverse reactions associated with bacterial or other microbial growth. There is also a need to produce the aforementioned contact lenses in the following way: this method adapts the transparency of the lens to be apparent to a user through the lens. The present invention meets these needs as follows.

Detailed Description

The invention includes a method of making an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, wherein the method comprises, consists essentially of, or consists of:

(a) treating the cured lens with a salt precursor; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.

The term "antimicrobial lens" as used herein refers to a lens having one or more of the following properties: inhibiting adhesion of bacteria or other microorganisms to the lens, inhibiting growth of bacteria or other microorganisms on the lens, and killing bacteria or other microorganisms on the surface of the lens or in the area surrounding the lens. For purposes of the present invention, bacteria or other microorganisms that adhere to the lens, bacteria or other microorganisms that grow on the lens, and bacteria or other microorganisms present on the surface of the lens are collectively referred to as a "microbial population". Preferably, lenses of the invention reduce viable bacteria or other microorganisms by at least about 0.25log, more preferably by at least about 0.5log, and most preferably by at least about 1.0log (90% inhibition). Such bacteria or other microorganisms include, but are not limited to, those found in the eye, particularly Pseudomonas aeruginosa (Pseudomonas aeruginosa), Acanthamoeba species, Staphylococcus aureus (Staphylococcus aureus), escherichia coli (escherichia coli), Staphylococcus epidermidis (Staphylococcus epidermidis), and Serratia marcescens (Serratia marcescens).

The term "metal salt" as used herein means having the general formula [ M]_a[X]_bWherein X comprises any negatively charged ion, a.gtoreq.1, b.gtoreq.1, and M is any positively charged metal selected from, but not limited to: al (Al)⁺³、Co⁺²、Co⁺³、Ca⁺²、Mg⁺²、Ni⁺²、Ti⁺²、Ti⁺³、Ti⁺⁴、V⁺²、V⁺³、V⁺⁵、Sr⁺²、Fe⁺²、Fe⁺³、Ag⁺²、Ag⁺¹、Au⁺²、Au⁺³、Au⁺¹、Pd⁺²、Pd⁺⁴、Pt⁺²、Pt⁺⁴、Cu⁺¹、Cu⁺²、Mn⁺²、Mn⁺³、Mn⁺⁴、Zn⁺²And the like. Examples of X include, but are not limited to, CO₃ ^-2、NO₃ ^-1、PO₄ ^-3、Cl^-1、I^-1、Br^-1、S^-2、O^-2And the like. Other X's include negatively charged ions, including CO₃ ^-2、NO₃ ^-1、PO₄ ^-3、Cl^-1、I^-1、Br^-1、S^-2And O^-2Etc., such as C_1-5Alkyl group CO₂ ^-1. The term metal salt as used herein does not include the zeolite disclosed in WO 03/011351. This patent application is incorporated herein by reference in its entirety. Preferably a is 1, 2 or 3. Preferably b is 1, 2 or 3. The preferred metal ion is Mg⁺²、Zn⁺²、Cu⁺¹、Cu⁺²、Au⁺²、Au⁺³、Au⁺¹、Pd⁺²、Pd⁺⁴、Pt⁺²、Pt⁺⁴、Ag⁺²And Ag⁺¹. A particularly preferred metal ion is Ag⁺¹. Examples of suitable metal salts include, but are not limited to, manganese sulfide, zinc oxide, zinc sulfide, copper sulfide, and copper phosphate. Examples of silver salts include, but are not limited to, nitrates, silver sulfate, silver iodide, silver carbonate, silver phosphate, silver sulfide, silver chloride, silver bromide, silver iodide, and silver oxide. Preferred silverThe salt is silver iodide, silver chloride and silver bromide. The lenses of the invention are ophthalmic lenses (these lenses are described in detail below), and the transparency of the lenses is of interest to the user. To produce lenses with transparency suitable for ophthalmic purposes, it is preferred that the metal salt particles have a diameter of less than about 10 microns (10 μm), more preferably less than about 1 μm, and even more preferably less than about 400 nm. The particle size of the metal salt in the antimicrobial lens can be determined by the following test.

Samples for scanning electron microscopy ("SEM") were prepared for profile analysis by mounting the entire lens vertically in an aluminum holder 25mm in diameter, which had been cut in half and drilled and tapped with two machine screws to clamp the sample. The lens is clamped so that half of the material is on the bench surface. The lens was then cut in half in a smooth stroke using a clean single-edged razor to avoid tearing the cut surface. These samples were then carbon coated in a vacuum evaporator to ensure conductivity. The distal ends of these samples were coated with colloidal carbon paint to ensure better conductivity.

Samples for surface analysis were prepared by taking the remaining half-lens and cutting a strip from close to the diameter, then placing the strip carefully on a bench of 25mm diameter with the concave side facing up, and two double-sided carbon "tapes" (stick tabs) on the top surface. The lens surface was also analyzed on a convex surface using the following method, with the remaining chordal convex side of the lens material also mounted on two "tapes". In both cases, the contact lens was flattened onto a carbon "tape" using a clean teflon material (0.032 inches thick). These samples were also coated with 20-40nm of spectrally pure graphite in a carbon vacuum evaporator. The distal ends of these samples were coated with colloidal carbon paint to ensure better conductivity.

Three images (left, center and right) were taken for the convex and concave surfaces of each lens at various magnifications. The sectional images were taken at 5000 x and 12,500 x magnification. For each position of the lens sheet (left, center or right), about 5-10 images are taken from the convex end to the concave end of the lens, depending on the thickness of the lens. The images were "stitched" together to obtain information on the particle size and distribution of silver iodide within the lens.

Particle size distribution measurements of surfaces and sections were obtained from 5000-fold images using Scion image analysis software. Results were obtained from three lenses per batch.

All images can be taken using a 5kV beam. Although both Secondary Electron (SE) and backscattered electron (BSE) images were obtained, only BSE images at 5000 x magnification were used for particle size analysis due to the high contrast of silver iodide particles compared to the background.

The amount of metal in the lens calculated based on the total weight of the lens was determined. When the metal is silver, the preferred amount of silver is from about 0.00001 wt% (0.1ppm) to about 10.0 wt%, preferably from about 0.0001 wt% (1ppm) to about 1.0 wt%, most preferably from about 0.001 wt% (10ppm) to about 0.1 wt% of the dry weight of the lens. With respect to the metal salt added, the molecular weight of the metal salt determines the weight percentage of metal ions converted to metal salt. The preferred amount of silver salt is from about 0.00003 wt% (0.3ppm) to about 30.0 wt%, preferably from about 0.0003 wt% (3ppm) to about 3.0 wt%, most preferably from about 0.003 wt% (30ppm) to about 0.3 wt% of the dry weight of the lens.

The term "salt precursor" refers to any compound or composition containing a cation that can be substituted with a metal ion. The concentration of the salt precursor in the solution thereof is from about 0.00001 to about 10.0 wt% (0.1 to 100,000ppm), more preferably from about 0.0001 to about 1.0 wt% (1 to 10,000ppm), most preferably from about 0.001 to about 0.1 wt% (10 to 1000ppm), based on the total weight of the solution. Examples of salt precursors include, but are not limited to, inorganic molecules such as sodium chloride, sodium iodide, sodium bromide, sodium sulfide, lithium chloride, lithium iodide, lithium bromide, lithium sulfide, potassium bromide, potassium chloride, potassium sulfide, potassium iodide, rubidium bromide, rubidium chloride, rubidium sulfide, cesium iodide, cesium bromide, cesium chloride, cesium sulfide, calcium chloride, calcium bromide, calcium iodide, calcium sulfide, magnesium chloride, magnesium bromide, magnesium iodide, magnesium sulfide, sodium tetrachloroargentate (sodium tetrachloroargentate), and the like. Examples of organic molecules include, but are not limited to, tetraalkylammonium lactate, tetraalkylammonium sulfate, quaternary ammonium halides such as tetraalkylammonium chloride, tetraalkylammonium bromide, or tetraalkylammonium iodide. Preferred salt precursors are selected from the group consisting of sodium chloride, sodium iodide, sodium bromide, lithium chloride, lithium sulfide, sodium sulfide, potassium iodide, and sodium tetrachloroargentate, and a particularly preferred salt precursor is sodium iodide.

The term "metal agent" refers to any composition (including aqueous solutions) comprising metal ions. Examples of such compositions include, but are not limited to, aqueous or organic solutions of silver nitrate, silver triflate, silver acetate, silver tetrafluoroborate, silver sulfate, zinc acetate, zinc sulfate, copper acetate, and copper sulfate, wherein the concentration of the metal agent in the solution is about 1 μ g/ml or greater. The preferred metal agent is an aqueous silver nitrate solution, wherein the concentration of silver nitrate in the solution is from about 0.0001 to about 2 weight percent (1ppm to 20,000ppm) of the total weight of the solution, more preferably from about 0.001 to about 0.1 weight percent (10ppm to 1,000ppm) of the total weight of the solution. The term "treating" refers to any method of contacting a metal agent or salt precursor with a lens, wherein the preferred method is dipping the lens in a solution of the metal agent or salt precursor. The treatment may comprise heating the lens in a solution of a metal agent or salt precursor, but is preferably carried out at ambient temperature. The duration of the treatment may last from about 30 seconds to about 24 hours, preferably from about 30 seconds to about 15 minutes.

The term "dispersant" as used herein refers to a composition that can be used to modulate the interaction between a polymer and a particle, particularly a metal salt mixed with the polymer. Examples of dispersants include, but are not limited to, polyvinylpyrrolidone ("PVP"), polyvinyl alcohol ("PVA") and derivatives, glycerol, and polyethylene oxide ("PEO"). Other dispersants that can be used are nitrogen-containing polymers such as, but not limited to, poly (dimethylacrylamide), poly (N-vinyl-N-methylacetamide). Certain non-polymeric materials containing nitrogen and/or sulfur may also be used as dispersants, such as cysteine, methionine, sodium sulfide, sodium thiosulfate, sodium thiocyanate. A particularly preferred dispersant is PVP. PVP of various molecular weights are commercially available. The K system is used to distinguish PVP of one molecular weight from PVP of another molecular weight. The preferred value of K is K90. The dispersant and metal agent are preferably mixed together with a suitable solvent (e.g., water, deionized water, alcohols, and mixtures thereof) to obtain a clear solution of those ingredients. If the metal agent is contained in an aqueous solution, the preferred amount of dispersant in the solution is from about 0.1% to about 50%, more preferably from about 4% to about 10%, even more preferably from about 2.5% to about 6%, and most preferably about 5%. In some embodiments, the molar ratio of dispersant units (dispersing agent units) to metal agent is at least about 1.5, at least about 2, and in some embodiments, at least about 4.

It is believed that the dispersant in the metal agent solution forms a complex with the metal agent. In this embodiment, it is desirable that the metal agent be substantially complexed with the dispersing agent before the metal agent solution is combined with the cured lens. By "substantially complexed" is meant that substantially all of the metal ion has been complexed with at least one dispersant. By "substantially all" is meant that at least about 90%, and in some embodiments, at least about 95% of the metal ions have been complexed with at least one dispersant.

The time to complex formation can be monitored in solution by spectroscopy (e.g., by UV-VIS or FTIR). The spectra of the metal reagent solution without dispersant were measured. The spectrum of the metal reagent solution is monitored after the addition of the dispersant, and the spectral change is monitored. The time at which the complex is formed is the time at which the spectral change is stationary.

Alternatively, the complexation time may be measured experimentally by forming a series of metal reagent-dispersant solutions having the same concentration, allowing each solution to mix for a different time, and mixing the metal reagent-dispersant solutions with the salt precursor solution in batches. When the metal reagent and salt precursor solution are poured directly together without control of the addition rate, the metal reagent-dispersant solution mixed for the complexation time will form a clear solution.

Complexing conditions include complexing time (as described above), temperature, ratio of dispersant to metal agent, and agitation rate. Increasing the temperature, molar ratio of dispersant to metal reagent, and agitation rate decreases the complexation time. With reference to the teachings of the present invention, one skilled in the art can vary the conditions to achieve the disclosed levels of complexation.

The term "lens" as used herein refers to an ophthalmic device that resides in or on the eye. These devices can provide any of the following effects: vision correction, wound care, drug delivery, diagnostic function, cosmetic enhancement, and the like. The term lens includes, but is not limited to, soft contact lenses, hard contact lenses, intraocular lenses, overlay lenses, ocular inserts, and optical inserts. Soft contact lenses are made from silicone elastomers or hydrogels, including but not limited to silicone hydrogels and fluorohydrogels.

For example, the term lens includes, but is not limited to, those made from the soft contact lens formulations described in US5,710,302, WO 9421698, EP 406161, JP 2000016905, US5,998,498, U.S. patent application 09/532,943, US 6,087,415, US5,760,100, US5,776,999, US5,789,461, US5,849,811, and US5,965,631. In addition, the metal salts of the present invention may be incorporated into commercial soft contact lenses. Examples of soft contact lens formulations include, but are not limited to, etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, galyfilcon A, senofilcon A, and lotrafilcon A formulations. Preferred lens formulations are etafilcon a, balafilcon a, acquafilcon a, galyfilcon a, lotrafilcon a and silicone hydrogels as prepared in US5,998,498, U.S. patent application serial No. 09/532,943 (a continuation-in-part of U.S. patent application 09/532,943 filed on 8/30/2000), WO 03/22321, US 6,087,415, US5,760,100, US5,776,999, US5,789,461, US5,849,811 and US5,965,631. These patents, as well as all other patents disclosed in this paragraph, are incorporated herein by reference in their entirety.

The metal salt is preferably added to a lens made from the silicone hydrogel component. The silicone-containing component is a component that contains at least one [ -Si-O-Si ] group in a monomer, macromer or prepolymer. Preferably, the amount of Si and associated O present in the silicone-containing component is greater than 20 weight percent of the total molecular weight of the silicone-containing component, more preferably greater than 30 weight percent of the total molecular weight of the silicone-containing component. Useful silicone-containing ingredients preferably contain polymerizable functional groups such as acrylate, methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinyl amide, and styryl functional groups. Examples of silicone ingredients that may be included in the silicone hydrogel formulation include, but are not limited to, silicone macromers, prepolymers, and monomers. Examples of polysiloxane macromers include, but are not limited to, polydimethylsiloxanes methacrylated with pendant hydrophilic groups as described in U.S. Pat. nos. 4,259,467, 4,260,725, and 4,261,875; polydimethylsiloxane macromers containing polymerizable functional groups as described in U.S. Pat. nos. 4,136,250, 4,153,641, 4,189,546, 4,182,822, 4,343,927, 4,254,248, 4,355,147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,605,712, 4,543,398, 4,661,575, 4,703,097, 4,837,289, 4,954,586, 4,954,587, 5,346,946, 5,358,995, 5,387,632, 5,451,617, 5,486,579, 5,962,548, 5,981,615, 5,981,675, and 6,039,913; polysiloxane macromers incorporating hydrophilic monomers, such as those described in U.S. Pat. Nos. 5,010,141, 5,057,578, 5,314,960, 5,371,147 and 5,336,797; macromonomers containing polydimethylsiloxane blocks and polyether blocks, such as those described in U.S. Pat. Nos. 4,871,785 and 5,034,461; combinations thereof, and the like. All patents cited herein are incorporated by reference in their entirety.

Polysiloxane-containing and/or fluorine-containing macromers described in U.S. Pat. Nos. 5,760,100, 5,776,999, 5,789,461, 5,807,944, 5,965,631 and 5,958,440 may also be used. Suitable polysiloxane monomers include tris (trimethylsiloxy) silylpropyl methacrylate, hydroxy-functional polysiloxane-containing monomers such as 3-methacryloxy-2- (hydroxypropoxy) propyl bis (trimethylsiloxy) methylsilane, and those disclosed in WO 03/22321, as well as mPDMS-containing monomers or siloxane monomers described in U.S. Pat. Nos. 4,120,570, 4,139,692, 4,463,149, 4,450,264, 4,525,563, 5,998,498, 3,808,178, 4,139,513, 5,070,215, 5,710,302, 5,714,557, and 5,908,906.

Other suitable siloxane-containing monomers include amide analogs of TRIS as described in US 4,711,943, vinyl carbamate or vinyl carbonate analogs as described in US5,070,215, monomers contained in US 6,020,445, monomethacryloxypropyl terminated polydimethylsiloxane, 3-methacryloxypropylbis (trimethylsiloxy) methylsilane, methacryloxypropylpentamethyldisiloxane, and combinations thereof.

In addition to soft contact lens formulations, hard contact lenses may also be used. Examples of hard contact lens formulations are made from polymers including, but not limited to: polymethyl methacrylates, silicon-containing acrylates, silicone acrylates, fluorine-containing ethers, polyacetylenes and polyimides, of which the preparation of representative examples can be found in JP 200010055, JP 6123860 and us patent 4,330,383. The intraocular lens of the present invention can be formed using known materials. For example, the lens may be made of a rigid material including, but not limited to, polymethylmethacrylate, polystyrene, polycarbonate, and the like, and combinations thereof. Further, flexible materials may be used, including but not limited to hydrogels, silicone materials, acrylic materials, fluorocarbon materials, and the like, or combinations thereof. Typical intraocular lenses are described in WO 0026698, WO0022460, WO 9929750, WO 9927978, WO 0022459, JP 2000107277 and US 4,301,012, 4,872,876, 4,863,464, 4,725,277, 4,731,079. All references mentioned in this application are incorporated herein by reference in their entirety.

It has been found that when metal salts are incorporated in accordance with the teachings of the present invention, ophthalmic devices are produced that are substantially free of undesirable haze. Preferably, the lenses of the invention are optically transparent, with optical clarity comparable to that of various lenses (e.g., lenses made from etafilcon A, genfilcon A, galyfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, and lotrafilcon A). In particular, the lenses of the invention have a% haze of less than about 200%, preferably less than about 150%, more preferably less than about 100%, even more preferably less than 30%, and even more preferably between less than about 30% and about 9%.

The% haze was measured using the following method. The test lenses hydrated in borate buffered saline (SSPS) were placed on a flat black background at ambient temperature in a clear 20 x 40 x 10mm glass chamber, illuminated from below with a fiber optic lamp (Titan Tool Supply co. fiber optic lamp, 0.5 inch diameter light guide, power setting 4-5.4) at an angle of 66 ° to the direction perpendicular to the lens chamber, and the images of the lenses were captured from above perpendicular to the lens chamber using a 14mm video camera (DVC 1300C: 19130RGB camera with Navitar TV Zoom 7000 Zoom lens) placed above the lens platform. Background scatter was subtracted from lens scatter using EPIX XCAP V1.0 software by subtracting the image of the blank cell. CSI Thin of-1.00 diopters by integration at 10mm at the center of the lens, followed by an arbitrarily set haze value of 100In comparison, the haze value was set to 0 without a lens, and the subtracted scattered light image was quantitatively analyzed. Five lenses were analyzed and the results averaged to give a% haze value calculated based on standard CSI lenses.

The term "cured" refers to any process used to react a mixture of lens components (i.e., monomers, prepolymers, macromers, etc.) to form a lens. The lens may be cured by light or heat. The preferred curing method is radiation, preferably UV radiation or visible light radiation, most preferably using visible light radiation. The lens formulations of the present invention can be formed by any method known to those skilled in the art (e.g., shaking or stirring) and used to form polymeric articles or devices by known methods.

For example, the antimicrobial lenses of the invention can be prepared as follows: the active ingredient and any diluent are mixed with the polymerization initiator and cured by appropriate conditions to form a product which can be subsequently formed into an appropriate shape by turning, cutting, etc. Alternatively, the reaction mixture may be placed in a mold and subsequently cured into a suitable article.

Various processes are known for processing lens formulations in the production of contact lenses, including spin casting and static casting. Spin casting processes are disclosed in US 3,408,429 and 3,660,545, and static casting processes are disclosed in US 4,113,224 and 4,197,266. The preferred method of producing the antimicrobial lenses of the invention is molding. In the case of hydrogel lenses, for this method, the lens formulation is placed in a mold having the general shape of the final desired lens and the lens formulation is subjected to conditions such that the various components polymerize to produce a hardened disc, which is subjected to various processing steps, including treating the polymerized lens with a liquid (e.g., water, inorganic salts, or organic solutions) to swell, or otherwise equilibrating the lens prior to enclosing the lens in its final package. These methods are further described in U.S. Pat. nos. 4,495,313, 4,680,336, 4,889,664, and 5,039,459, which are incorporated herein by reference. For the purposes of the present invention, polymerized lenses that are not swollen or otherwise equilibrated are considered cured lenses.

Further, the invention includes a method of making an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, wherein the method comprises, consists essentially of, or consists of:

(a) treating the cured lens with a metal agent and a dispersant; and

(b) treating the lens of step (a) with a salt precursor.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges.

Still further, the invention includes a method of making an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, wherein the method comprises, consists essentially of, or consists of:

(a) treating the cured lens with a metal agent and a dispersant; and

(b) treating the lens of step (a) with a salt precursor and a dispersant.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges. The dispersants of steps (a) and (b) may be the same or different, but are preferably the same.

Still further, the invention includes a method of making an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, wherein the method comprises, consists essentially of, or consists of:

(a) treating the cured lens with a salt precursor and a dispersant; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges. The dispersants of steps (a) and (b) may be the same or different, but are preferably the same.

Still further, the invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, made by a process wherein the process comprises, consists essentially of, or consists of the steps of:

(a) treating the cured lens with a metal agent and a dispersant; and

(b) treating the lens of step (a) with a salt precursor.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges.

Still further, the invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, made by a method comprising, consisting essentially of, or consisting of:

(a) treating the cured lens with a salt precursor; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges.

Still further, the invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, made by a process wherein the process comprises, consists essentially of, or consists of the steps of:

(a) treating the cured lens with a metal agent and a dispersant; and

(b) treating the lens of step (a) with a salt precursor and a dispersant.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges. The dispersants of steps (a) and (b) may be the same or different, but are preferably the same.

Still further, the invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, made by a method comprising, consisting essentially of, or consisting of:

(a) treating the cured lens with a salt precursor and a dispersant; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.

The terms antimicrobial lens, metal salt, salt precursor, metal agent, dispersant and treatment all have their aforementioned meanings and preferred ranges. The dispersants of steps (a) and (b) may be the same or different, but are preferably the same.

Although haze is a measure of the transparency of a lens, the overall transparency of the lens may be low, but may contain deposited metallic agents in localized areas ("localized area deposition"). One of the advantages of the lens and the method for producing the same of the present invention is the reduction of localized areas of deposition. This can be confirmed with a dark field microscope according to the following method.

The hydration test lenses to be examined were placed in a crystallization dish available from KimbleGlass, Inc. [ KIMAX 230005035, 50X 35mm ]. A borate buffered sodium sulfate solution (SSPS, 10-12ml) that had been filtered through a ≦ 0.45 μm filter was added to the pan. Placing the lens close to the center of the disc minimizes artifacts (artifacts) due to reflected light. The test was performed using a Nikon SMZ 1500 microscope. The disc containing the lenses is placed on a light stage. The light source was set to maximum intensity and the microscope was set in D.F. (dark field) mode. The aperture on the microscope is fully opened. The software used to capture the images was called 'Aquiento, by http:// www.olympus-sis.com/mercy', (formerly Aquiento). Images were captured using a NikonDXM1200F digital camera with the following settings (settings in the program Aquinto): the 'exposure time' 53.0555ms, 'color filter' gray 'and' capture mode '960 × 768' deselect 'horizontal Mirror image (mirrorhot)', 'vertical Mirror image (mirrorvert)', 'Logarithmic exposure (Logarithmic)' and 'Auto refresh)'. Under the ' Optimize ' column (in program Aquinto), all filters are set to ' no filter ' (Nofilter) '. The captured images are evaluated for areas of localized deposition.

In order to illustrate the invention, the following examples are given. These examples do not limit the invention. These examples are intended only to suggest a method of practicing the invention. Those skilled in the art of contact lenses and others skilled in the art may find other ways to practice the present invention. However, those methods are considered to be within the scope of the present invention.

Examples

The following abbreviations are used in the examples:

sodium Sulfate Packing Solution (SSPS)

The SSPS comprises the following in deionized water:

1.40 wt% sodium sulfate

0.185 wt% sodium borate [1330-43-4], Mallinckrodt

0.926 wt% boric acid [10043-35-3], Mallinckrodt

0.005 wt% methyl cellulose

Example 1

Preparation of antimicrobial lenses from cured lenses

The cured and hydrated galyfilcon a lenses were placed in a bottle containing a solution of 50ppm methylcellulose in sodium iodide in deionized water (about 3ml of solution per lens) and rolled overnight on a roller bottle machine. The lens was transferred from the bottle to a blister pack where the excess sodium iodide solution was removed. A solution of silver nitrate in deionized water (800 μ l) containing the appropriate dispersant was added to the blister for 2-5 minutes. The silver nitrate solution was removed and the lenses were placed in a bottle of deionized water and rolled on a roller bottle machine for about 30 minutes. The deionized water was replaced with borate buffered aqueous sodium sulfate solution (SSPS) containing 50ppm of methylcellulose and rolled on a roller bottle machine for an additional 30 minutes. The solution was then replaced with fresh SSPS.

The lenses were then transferred to a new blister and 950. mu.l SSPS was dosed. The blisters were sealed and autoclaved at 125 ℃ for 18 minutes, and analyzed for haze using the methods described herein and silver content using the methods described below. The results are shown in Table 1. The data show that the addition of a dispersant reduces the% haze or improves the haze uniformity from lens to lens, as evidenced by the reduction in standard deviation.

The silver content of the lens after autoclaving the lens was determined by instrumental neutron activation analysis "INAA". INAA is a qualitative and quantitative elemental analysis method based on the artificial induction of specific radionuclides by irradiation with protons in a nuclear reactor. After irradiation of the sample, the characteristic gamma rays emitted by radionuclide decay are quantitatively measured. The detected gamma rays of a particular energy indicate the presence of a particular radionuclide, resulting in a high degree of specificity. Becker, d.a.; greenberg, r.r.; stone, s.f.j.radio.nuclear.chem.1992, 160(1), 41-53; becker, d.a.; anderson, d.l.; lindstrom, r.m.; greenberg, r.r.; garrity, k.m.; mackey, e.a.j.radio.nuclear.chem.1994, 179(1), 149-54. The INAA procedure for the quantitative determination of the silver content in contact lens materials uses the following two nuclear reactions:

1. in the activation reaction, after capturing radioactive neutrons generated in the nuclear reactor, the neutrons are stabilized¹⁰⁹Ag (isotopic abundance 48.16%) production¹¹⁰Ag。

2. In the decay reaction, the reaction mixture is mixed,¹¹⁰Ag(τ^1/224.6 seconds) decays mainly with the energy characteristic of the radionuclide (657.8keV) by negative electron emission proportional to the initial concentration. .

Measurement of gamma-ray emission by gamma-ray spectroscopy (a well-established pulse-height technique) combined with that produced by irradiated standards and samples¹¹⁰The Ag decay is specific and results in a measure of the analyte concentration.

TABLE 1

% dispersing agent	NaIppm	AgNO3Soaking time (minutes)	AgNO3ppm	Ag(μg)	Standard deviation (ug)	Haze (% relative to CSI)	Standard deviation (% relative to CSI)
								Is free of	1100	2	700	17.8	0.2	42.3	14.0
Is free of	1100	2	700	18.8	0.3	48.4	11.0
								Is free of	1100	2	700	15.8	2.1	22	5.74
1％PVP K-90	1100	2	700	17.8	0.7	23.3	0.8
								1％PVP K-90	1100	2	700	17.8	0.6	22.7	1.4
2.5％PVP K-90	1500	3	950	24.1	0.8	24.0	1.3
								2.5％PVP K-90	1500	3	950	23.8	0.5	21.5	1.1
2.5％PVP K-90	1100	3	700	16.3	2.5	22.7	1.0
								2.5％PVP K-90	1100	3	700	17.1	0.4	23.4	1.1
5％PVP K-90	1100	3	700	17.8	1.8	22.7	1.2
								5％PVP K-90	1100	3	700	18.2	1.3	23.5	1.0
5％PVP K-12	1100	3	700	16.7	1.1	18.4	1.5
								10％PVP K-12	1100	3	700	16.5	0.5	14.1	1.3
15％PVP K-12	1100	3	700	17.0	1.3	14	1.8
								5％PEO 10K	1100	3	700	17.9	1.5	18.8	3.4
10％PEO 10K	1100	3	700	17.4	1.7	22	6.1
								25％GLY	1100	3	700	17.4	0.4	28.6	5.4
6％PVA40K	1100	3	700	18.0	1.3	26.5	5.4
								4％PVA 120K	1100	3	700	17.9	0.7	17.4	2.6
5％PVP K-90	1100	3	700	18.0	1.2	14.2	1.6

The abbreviations PVA are polyvinyl alcohol, PEO is polyethylene oxide, GLY is glycerol, PVP is polyvinylpyrrolidone

Claims (25)

1. A method of making an antimicrobial lens comprising a metal salt, wherein the method comprises the steps of:

(a) treating the cured lens with a salt precursor; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.

2. The method of claim 1, wherein the dispersant is selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, glycerin, and polyethylene oxide.

3. The method of claim 1 wherein said dispersant is selected from the group consisting of PVP K-12, PVPK-30, PVP K-60 and PVP K-90.

4. The method of claim 1, wherein the dispersant is PVP K-90.

5. The method of claim 1, wherein the salt precursor is selected from the group consisting of sodium chloride, sodium iodide, potassium iodide, sodium bromide, lithium chloride, lithium sulfide, sodium sulfide, potassium sulfide, sodium tetrachloro argentate, tetraalkylammonium lactate, tetraalkylammonium sulfate, tetraalkylammonium chloride, tetraalkylammonium bromide, and tetraalkylammonium iodide.

6. The method of claim 1, wherein the salt precursor is sodium iodide.

7. The method of claim 1, wherein the metal agent is selected from the group consisting of silver tetrafluoroborate, silver sulfate, zinc acetate, zinc sulfate, copper acetate, and copper sulfate.

8. The method of claim 1, wherein the metal agent is silver nitrate.

9. The method of claim 1, wherein the metal salt is selected from the group consisting of manganese sulfide, zinc oxide, zinc sulfide, copper phosphate, silver nitrate, silver sulfate, silver iodate, silver carbonate, silver phosphate, silver sulfide, silver chloride, silver bromide, silver iodide, and silver oxide.

10. The method of claim 1, wherein the metal salt is selected from the group consisting of silver nitrate, silver sulfate, silver iodate, silver carbonate, silver phosphate, silver sulfide, silver chloride, silver bromide, silver iodide, and silver oxide.

11. The method of claim 1, wherein the metal salt is silver iodide.

12. A method of making an antimicrobial lens comprising a metal salt, wherein the method comprises the steps of:

(a) treating the cured lens with a metal agent and a dispersant; and

(b) treating the lens of step (a) with a salt precursor.

13. The method of claim 12, wherein the dispersant is selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, glycerin, and polyethylene oxide.

14. The method of claim 12, wherein said dispersant is selected from the group consisting of PVP K-12, PVPK-30, PVP K-60 and PVP K-90.

15. The method of claim 12, wherein the dispersant is PVP K-90.

16. The method of claim 12, wherein the salt precursor is selected from the group consisting of sodium chloride, sodium iodide, sodium bromide, lithium chloride, lithium sulfide, potassium iodide, sodium sulfide, potassium sulfide, sodium tetrachloro argentate, tetraalkylammonium lactate, tetraalkylammonium sulfate, tetraalkylammonium chloride, tetraalkylammonium bromide, and tetraalkylammonium iodide.

17. The method of claim 12, wherein the salt precursor is sodium iodide.

18. The method of claim 12, wherein the metal agent is selected from the group consisting of silver nitrate, silver triflate, silver acetate, silver tetrafluoroborate, silver sulfate, zinc acetate, zinc sulfate, copper acetate, and copper sulfate.

19. The method of claim 12, wherein the metal agent is silver nitrate.

20. The method of claim 12, wherein the metal salt is selected from the group consisting of manganese sulfide, zinc oxide, zinc sulfide, copper phosphate, silver nitrate, silver sulfate, silver iodate, silver carbonate, silver phosphate, silver sulfide, silver chloride, silver bromide, silver iodide, and silver oxide.

21. The method of claim 12, wherein the metal salt is selected from the group consisting of silver nitrate, silver sulfate, silver iodate, silver carbonate, silver phosphate, silver sulfide, silver chloride, silver bromide, silver iodide, and silver oxide.

22. The method of claim 12, wherein the metal salt is silver iodide.

23. A method of making an antimicrobial lens comprising a metal salt, wherein the method comprises the steps of:

(a) treating the cured lens with a metal agent and a dispersant; and

(b) treating the lens of step (a) with a salt precursor and a dispersant.

24. A method of making an antimicrobial lens comprising a metal salt, wherein the method comprises the steps of:

(a) treating the cured lens with a salt precursor and a dispersant; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.

25. An antimicrobial lens comprising a metal salt, said antimicrobial lens prepared by a process, wherein said process comprises the steps of:

(a) treating the cured lens with a salt precursor; and

(b) treating the lens of step (a) with a dispersing agent and a metal agent.