HK1139337A - Antimicrobial contact lenses with reduced haze and preparation thereof - Google Patents

Description

Antimicrobial contact lenses with low haze and preparation thereof

RELATED APPLICATIONS

This application is a non-provisional proposal for U.S. serial No. 60/863,709 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 to improve vision since the fifties of the twentieth century. The first contact lenses were made of hard materials. The patient was used during non-sleep time and removed from the wash. Current developments in this area have resulted in soft contact lenses that can be worn continuously for several days or longer without the need for removal for cleaning. Although many patients prefer these lenses for increased comfort, these lenses can cause some adverse reactions to the user. Continued use of the lens may promote the accumulation of bacteria or other microorganisms, particularly Pseudomonas aeruginosa, on the surface of the soft contact lens. The accumulation of bacteria or other microorganisms can cause harmful adverse effects such as acute pinkeye in contact lenses and the like. Although the problem of bacteria and other microorganisms is closely related to the continuous use of soft contact lenses, the accumulation of bacteria and other microorganisms also occurs in hard contact lens wearers.

Us patent 5,820,918 discloses medical devices made from water-absorbent polymer materials having medical compounds with low solubility in aqueous solutions, such as preserved or radiopaque compounds. However, the methods disclosed in the examples produce opaque devices that are not suitable for ophthalmic devices such as contact lenses.

Accordingly, there is a need to produce contact lenses that inhibit the growth of bacteria or other microorganisms and/or the adhesion of bacteria or other microorganisms to 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 lens. 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 following invention satisfies these needs.

Brief Description of Drawings

Fig. 1 shows the relationship between molar ratio and haze.

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 solution comprising a salt precursor; and

(b) treating the lens of step (a) with a solution comprising a metal agent,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

The term "antimicrobial lens" as used herein refers to a lens that exhibits one or more of the following characteristics: inhibiting adhesion of bacteria or other microorganisms to the lens; inhibit the growth of bacteria or other microorganisms on the lens, and kill bacteria or other microorganisms on the surface of the lens or in the area surrounding the lens. For the purposes of the present invention, adhesion of bacteria or other microorganisms to the lens, growth of bacteria or other microorganisms on the lens, and presence of bacteria or other microorganisms on the lens surface are collectively referred to as "microbial populations". Preferably, the lenses of the invention exhibit a reduction in viable bacteria or other microorganisms of at least about 0.25log, more preferably at least about 0.5log, and most preferably at least about 1.0log (. gtoreq.90% inhibition). Such bacteria or other microorganisms include, but are not limited to, those found in the eye, particularly Pseudomonas aeruginosa (Pseudomonas aeruginosa), Acanthamoebaceae (Acanthamoebacteria), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Escherichia coli), Staphylococcus epidermidis (Staphylococcus epidermidis), and Serratia marcescens (Serratia marcens).

As used herein, the term "metal salt" refers to a salt having the general formula [ M]_a[X]_bWherein X contains any negatively charged ion, a.gtoreq.1, b.gtoreq.1, M is any positively charged metal selected from, but not limited to: al (Al)⁺³、Co⁺²、Co⁺³、Ca⁺、Mg⁺²、Ni⁺²、Ti⁺²、Ti⁺³、Ti⁺⁴、V⁺²、V⁺³、V⁺⁵、Sr⁺²、Fe⁺²、Fe⁺³、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 so on. 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 so on. X also comprises a compound containing CO₃^-2 NO₃^-1、PO₄^-3、Cl^-1、I^-1、Br^-1、S^-2、O^-2Etc. negatively charged ions, e.g. C_1-5Alkyl group CO₂^-1. The term metal salt as used herein does not include the zeolites disclosed in WO 03/011351. This patent application is hereby incorporated by reference herein 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. Combination of Chinese herbsExamples 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, silver nitrate, silver sulfate, silver iodate, silver carbonate, silver phosphate, silver sulfide, silver chloride, silver bromide, silver iodide, and silver oxide. Preferred silver salts are 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 size of the particles in the lens can be measured by the following method.

Samples for scanning electron microscopy ("SEM") were prepared for profile analysis as follows: the entire lens was mounted vertically in a 25mm diameter aluminum holder which was cut in half and drilled and tapped into two mechanical screws to hold the sample. The lens is clamped so that half of the material is above the stage surface. The lens was then cut in half with a clean single-edged razor in a smooth stroke to avoid tearing the cut surface. The samples were then carbon coated in a vacuum evaporator to ensure conductivity. The distal end (far edge) of these samples was painted with a colloidal carbon paint to make the conductivity better.

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 with the concavity facing up on a jig of 25mm diameter with two double-sided carbon "tapes" (tack tab) 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 at different magnifications from the convex and concave surfaces of each lens. Sectional images were taken at magnifications of 5000x and 12,500 x. For each position of the lens sheet (left, center or right), about 5-10 images are taken according to the thickness of the lens, starting from the convex end to the concave end of the lens. The images were "stitched" together to obtain information on the silver iodide particle size and distribution inside the lens.

Particle size distribution measurements of the surface and cross-section were taken from the 5000x images using Scion image analysis software. The (complex) results were compiled from three lenses per batch.

All images were taken with a 5kV beam energy. Although both Secondary Electron (SE) images and backscattered electron (BSE) images can be obtained simultaneously, the particle size analysis was performed with only 5000x BSE images due to the high contrast obtained with silver iodide particles compared to the background.

The amount of metal in the lens was determined based on the total weight of the lens. When the metal is silver, the preferred silver content is from about 0.00001% (0.1ppm) to about 10.0% by weight, more preferably from about 0.0001% (1ppm) to about 1.0% by weight, and most preferably from about 0.001% (10ppm) to about 0.1% by weight, based on the dry weight of the lens. For the addition of metal salts, the molecular weight of the metal salt determines the weight percent of metal ions converted to metal salt. The preferred silver salt content is from about 0.00003% (0.3ppm) to about 30.0% by weight, preferably from about 0.0003% (3ppm) to about 3.0% by weight, and most preferably from about 0.003% (30ppm) to about 0.3% by weight of the dry weight of the lens.

The term "solution" refers to an aqueous or organic composition in which the salt precursor is dissolved. The preferred solution is water. The solution may contain buffer salts (e.g., sodium borate/boric acid), excipients, surfactants, wetting agents, and the like. 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 between about 0.00001 to about 10.0 weight percent (0.1 to 100,000ppm), more preferably between about 0.0001 to about 1.0 weight percent (1 to 10,000ppm), and most preferably between about 0.001 to about 0.1 weight percent (10 to 1,000ppm), 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 (e.g., tetraalkylammonium chloride, tetraalkylammonium bromide, tetraalkylammonium iodide). Preferred salt precursors are selected from: sodium chloride, sodium iodide, sodium bromide, lithium chloride, lithium sulfide, sodium sulfide, potassium iodide, potassium sulfide, potassium bromide, potassium chloride, sodium tetrachloroargentate, and a particularly preferred salt precursor is sodium iodide.

The term "metal agent" refers to any composition (including aqueous solutions) containing metal ions. Examples of such compositions include, but are not limited to: silver nitrate, silver triflate, or an aqueous or organic solution of silver acetate, silver sulfate, silver tetrafluoroborate, zinc acetate, zinc sulfate, copper acetate, copper sulfate, and the like, wherein the metal agent has a solubility in the solution of about 1 μ g/mL or more. The preferred metal agent is an aqueous silver nitrate solution wherein the concentration of silver nitrate in the solution is from about greater than or equal to 0.0001 to about 2 weight percent, more preferably from about greater than 0.001 to about 0.1 weight percent, based on the total weight of the solution. The term "treating" refers to any method of contacting a solution of a metal agent or salt precursor with a lens, wherein the preferred method is to immerse the lens in such a solution. 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 time of the treatment may last for any time point from about 30 seconds to about 24 hours, preferably from about 30 seconds to about 15 minutes.

The term molar ratio as used herein refers to the ratio of metal agent to salt precursor. It is calculated by the following method: the concentration (ppm) of the metal agent contained in the solution is divided by the molecular weight of the metal agent to obtain a first value, and the concentration (ppm) of the salt precursor contained in the solution is divided by the molecular weight of the salt precursor to obtain a second value. The ratio of the first value to the second value is the molar ratio. For example, if the metal agent is silver nitrate (500ppm, molecular weight 169.88), the salt precursor is sodium iodide (700ppm, molecular weight 149.89), the first value is 4.67, and the second value is 2.94. The molar ratio of these conditions was 0.63. To produce the lenses of the invention with suitable haze, it is preferred that the molar ratio is greater than about 0.2, more preferably greater than about 0.4, even more preferably from about 0.6 to about 2.4, and most preferably from about 0.6 to about 10.0.

The term "lens" as used herein refers to an ophthalmic device that is placed in or on the eye. These devices may provide vision correction, wound care, drug delivery, diagnostic functions, cosmetic enhancements or effects, or a combination of these properties. The term lens includes, but is not limited to, soft contact lenses, hard contact lenses, intraocular lenses (intraocular lenses), overlay lenses (overlay lenses), ocular inserts (ocular inserts), and optical inserts (optical inserts). Soft contact lenses are made from silicone rubbers or hydrogels, which include, but are not limited to, silicone hydrogels and fluorohydrogels (fluorohydrogels).

For example, the term lens includes, but is not limited to, those lenses made from the soft contact lens formulations described in US5,710,302, WO 9421698, EP406161, JP 2000016905, US5,998,498, U.S. patent application No. 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 can be added to commercial soft contact lenses. Examples of soft contact lens formulations include, but are not limited to, formulations of etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, galyfilcon A, senofilcon A, and lotrafilcon A. Preferred lens formulations are etafilcon A, balafilcon A, acquafilcon A, galyfilcon A, lotrafilcon A and organosilicone gels, the preparation of which is described in U.S. Pat. No. 5,998,498, U.S. patent application Ser. No. 09/532,943 (a continuation-in-part of U.S. Pat. No. 09/532,943 filed on 8/30/2000), WO03/22321, U.S. Pat. No. 5,6,087,415, U.S. Pat. No. 5,760,100, U.S. Pat. No. 5,776,999, U.S. Pat. No. 5,789,461, U.S. Pat. No. 5,849,811 and U.S. Pat. No. These patents, as well as others published in this paragraph, are incorporated herein by reference in their entirety.

The metal salt is preferably added to a lens made with 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 polysiloxane-containing component is greater than 20 weight percent, more preferably greater than 30 weight percent, of the total molecular weight of the polysiloxane-containing component. Useful silicone-containing components preferably contain polymerizable functional groups such as acrylate, methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinyl amide and styrene functional groups. Examples of silicone components contained in the silicone hydrogel formulation include, but are not limited to: polysiloxane 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 having polymerizable functional groups 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 comprising polydimethylsiloxane blocks and polyether blocks such as those described in U.S. Pat. Nos. 4,871,785 and 5,034,461; and combinations thereof, and the like. All patents cited herein are incorporated by reference in their entirety.

Polysiloxane-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 silicone monomers include tris (trimethylsiloxy) silylpropyl methacrylate, hydroxyl-functional silicone monomers such as 3-methacryloxy-2- (hydroxypropoxy) propyl bis (trimethylsiloxy) methylsilane and those disclosed in WO03/22321, and 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.

Additional suitable silicone-containing monomers include: amide analogs of TRIS described in US 4,711,943, vinyl carbamate or vinyl carbonate analogs described in US5,070,215, monomers contained in US 6,020,445, monomethacryloxypropyl terminated polydimethylsiloxane, 3-methacryloxypropyl bis (trimethylsiloxy) methylsilane, methacryloxypropyl pentamethyldisiloxane, 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 methacrylate, silicon-containing acrylates, silicone acrylates, fluorine-containing ethers, polyacetylenes, polyimides, of which the preparation of representative examples can be found in JP 200010055, JP 6123860 and US 4,330,383. The intraocular lens of the present invention can be prepared from 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. In addition, 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, WO 0022460, WO 9929750, WO 9927978, WO 0022459 and 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 clear, with optical clarity comparable to lenses made from the following formulations: etafilcon A, genfilcon A, galyfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A and lotrafilcon A. Specifically, the lenses of the invention have a% haze of less than about 200%, preferably less than about 150%, more preferably less than about 100%, more preferably less than about 60%, and even more preferably between less than about 50%.

The% haze was measured by the following method. Borate buffered saline (SSPS) containing hydrated test lenses was placed in a 20x 40x 10mm clear glass tank on a flat black background at ambient temperature, 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 66 ° to the direction perpendicular to the lens tank, and the images of the lenses were captured from vertically above the lens tank with a video camera (DVC 1300C: 19130 RGB camera with Navitar TV Zoom 7000 Zoom) located 14mm above the lens platform. The back scatter was subtracted from the lens scatter by subtracting the image of the blank groove with EPIX XCAP V1.0 software. By integrating the central 10mm of the lens and then comparing it with CSI Thin of-1.00 diopters(arbitrarily set to a haze value of 100) and no lens set to a haze value of 0, to quantitatively analyze the subtracted scattered light images. 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. Preferred curing methods are radiation, preferably UV radiation or visible radiation, most preferably visible radiation. The lens formulations of the present invention can be formed by any method known to those skilled in the art, such as 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 by: the reactive components and any diluents are mixed with the polymerization initiator and cured by appropriate conditions to form an article which can then be formed into an appropriate shape by turning, cutting, and the like. Or the reaction mixture may be placed in a mold and subsequently cured into a suitable article.

In the production of contact lenses, various processes are known for processing lens formulations, 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, conditions are applied to the lens formulation to polymerize the components to produce a hardened disc, and the disc is subjected to a number of different processing steps, including treating the polymerized lens with a liquid (such as water, inorganic salts, or organic solutions) to swell it, or otherwise equilibrating the lens and subsequently enclosing it in a 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 to be 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 solution comprising a metal agent; and

(b) treating the lens of step (a) with a solution comprising a salt precursor,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

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

In addition, the present invention also includes an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, the antimicrobial lens made by a process comprising, consisting essentially of, or consisting of:

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

(b) treating the lens of step (a) with a solution comprising a metal agent,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

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

In addition, the present invention also includes an antimicrobial lens comprising, consisting essentially of, or consisting of a metal salt, the antimicrobial lens made by a process comprising, consisting essentially of, or consisting of:

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

(b) treating the lens of step (a) with a solution comprising a salt precursor,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

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

Although haze is a measure of lens clarity, a lens may result in overall low clarity due to the localized area of the metallic agent containing the deposited metallic agent ("localized area of deposition"). One of the advantages of the lens of the invention and the method for producing it is to reduce the local area of deposition. This can be demonstrated by dark field microscopy according to the following method.

The hydration test lenses to be tested were placed in a chamber produced by Kimble Glass, Inc. [ KIMAX 230005035, 50x35mm]On the crystallization dish. Borate buffered sodium sulfate solution (SSPS, 10-12mL) filtered through ≦ 0.45um filter was added to the dish. The lens is placed close to the center of the dish to minimize artifacts (artifacts) in the resulting image of the reflected light. The test was performed using a Nikon SMZ 1500 microscope. The dish containing the lens was placed on a light stage. The light source was set to maximum intensity and the microscope was set to D.F. (dark field) mode. The microscope aperture is fully opened. The software for capturing images is called' byhttp://www.olympus-sis.com/The product was Aquinto' (formerly known as Aquinto). Images were captured using a Nikon DXM1200F digital camera at the following camera settings (set in the Aquinto program): the 'exposure time' is 53.0555ms, 'color filter' is 'gray,' capture mode 'is' 960x768 ', horizontal mirroring (mirrorhorrz)', 'vertical mirroring (mirrorvert)', 'Logarithmic exposure (Logarithmic)' and 'auto refresh' are deselected. All filter settings are set to 'no filter' under the 'optimize' column (in the Aquinto procedure). The captured image is evaluated for local deposition areas.

In order to illustrate the invention, the following examples are given. These examples do not limit the invention. They are used 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 and stock solutions are used in the examples.

Sodium Sulfate Packing Solution (SSPS)

The SSPS contains the following in deionized water:

1.40% by weight 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

Silver nitrate solution 700ppm

0.7g silver nitrate

1000mL of deionized water

Sodium iodide solution

1.1g sodium iodide

1000g deionized water (containing 50ppm methylcellulose)

Example 1

Antimicrobial lenses prepared from cured lenses

The cured and hydrated galyfilcon A lenses were placed in a bottle containing 1100ppm sodium iodide solution containing 50ppm methylcellulose (3 mL per lens, 1100 ug/mL). The lens is transferred from the bottle to a blister pack where excess sodium iodide solution is removed. A silver nitrate solution (800. mu.L of deionized water containing 700. mu.g/mL silver nitrate) was added to the blister over a period of 2-5 minutes. The silver nitrate solution was removed and the lenses were placed in a bottle containing deionized water and allowed to stand for about 30 minutes. The deionized water was replaced with fresh deionized water (DI water) and allowed to stand for an additional 30 minutes. The solution was then replaced with borate buffered sodium sulfate solution (SSPS). The lenses were transferred to blisters containing SSPS. The blisters were sealed and autoclaved at 125 ℃ for 18 minutes and analyzed for haze and silver content. The average silver content per lens was determined to be about 16.0 ug.

The silver content of the lens after high pressure treatment 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 neutron irradiation in a nuclear reactor. After irradiation of the sample, the characteristic gamma rays emitted by the decaying radionuclide are quantitatively measured. The detection of gamma rays of a particular energy indicates the presence of a particular radionuclide, which makes the degree of specificity high. 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 method 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 activated neutrons are stabilized¹⁰⁹Ag (isotopic abundance 48.16%) production¹¹⁰Ag。

2. In the course of the decay reaction, the reaction mixture,¹¹⁰Ag(τ^1/224.6 seconds) decays by negative electron emission proportional to the initial concentration, mainly at the energy characteristic of the radionuclide (657.8 keV). Measurement of the production of irradiated standards and samples by gamma-ray spectroscopy, a well-established technique for pulse height analysis¹¹⁰Ag decay specific gamma ray emission, yielding a measure of analyte concentration.

Example 2 high haze

Galyfilcon a lenses were treated according to the method of example 1 with a solution having the following concentrations: 5000ppm sodium iodide and 500ppm silver nitrate gave a silver content of 16.7. + -. 0.4mcg and a haze of 175.7. + -. 18.8% CSI. The molar ratio was 0.09.

Example 3 Low haze

Galyfilcon a lenses were treated according to the method of example 1 with a solution having the following concentrations: 1100ppm sodium iodide and 700ppm silver nitrate, to give a silver content of 16.0. + -. 0.3mcg and a haze of 37.6. + -. 7.8% CSI. The molar ratio was 0.56.

Example 4

Antimicrobial lenses prepared from cured lenses

The cured and hydrated galyfilcon A lenses were placed in a bottle containing a sodium iodide solution containing 50ppm methylcellulose (3 mL per lens). The lens was transferred from the bottle to a blister pack where excess sodium iodide solution was removed. Silver nitrate solution (800. mu.L) was added to the blister over 2-5 minutes (see Table 1 concentrations and times). The silver nitrate solution was removed and the lenses were placed in a bottle containing deionized water and allowed to stand for about 30 minutes. The deionized water was replaced with fresh deionized water (DI water) and allowed to stand for an additional 30 minutes. This solution was then replaced with borate buffered sodium sulfate solution (SSPS). The lenses were transferred to blisters containing SSPS. The blisters were sealed and treated at 125 ℃ for 18 minutes and analyzed for haze and silver content. FIG. 1 is a graphical representation of the data of Table 1. The graph shows that molar ratios of about 0.2 or higher reduce the% haze of the lens.

TABLE 1

Claims (16)

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

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

(b) treating the lens of step (a) with a solution comprising a metal agent,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

2. The process of claim 1 wherein said molar ratio is from about 0.2 to about 10.0.

3. The process of claim 1 wherein said molar ratio is from about 0.4 to about 2.4.

4. The process of claim 1 wherein said molar ratio is from about 0.6 to about 2.4.

5. The process of claim 1 wherein said molar ratio is from about 0.8 to about 2.4.

6. The method of claim 1 wherein the metal salt is silver iodide, the salt precursor is sodium iodide, and the metal agent is silver nitrate.

7. The process of claim 2 wherein said molar ratio is from about 0.2 to about 10.0.

8. A method of making a metal salt-containing antimicrobial lens, wherein the method comprises the steps of:

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

(b) treating the lens of step (a) with a solution comprising a salt precursor,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

9. The method of claim 8 wherein the metal salt is silver iodide, the salt precursor is sodium iodide, and the metal agent is silver nitrate.

10. The process of claim 9 wherein said molar ratio is from about 0.2 to about 10.0.

11. An antimicrobial lens comprising a metal salt, the antimicrobial lens made by a process comprising the steps of:

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

(b) treating the lens of step (a) with a solution comprising a metal agent,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

12. The antimicrobial lens of claim 11 wherein the metal salt is silver iodide, the salt precursor is sodium iodide, and the metal agent is silver nitrate.

13. The antimicrobial lens of claim 12 wherein the molar ratio is from about 0.2 to about 10.0.

14. An antimicrobial lens comprising a metal salt, the antimicrobial lens made by a process comprising the steps of:

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

(b) treating the lens of step (a) with a solution comprising a salt precursor,

wherein the ratio of the molar ratio of the metal reagent in solution to the molar ratio of the salt precursor in solution is greater than about 0.2.

15. The antimicrobial lens of claim 14 wherein the metal salt is silver iodide, the salt precursor is sodium iodide, and the metal agent is silver nitrate.

16. The antimicrobial lens of claim 15 wherein the molar ratio is from about 0.2 to about 10.0.