Classifications

• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
  • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
  • C08J7/12—Chemical modification
  • C08J7/123—Treatment by wave energy or particle radiation
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
  • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
  • G02B1/041—Lenses
  • G02B1/043—Contact lenses
• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B3/00—Simple or compound lenses
  • G02B3/0006—Arrays
  • G02B3/0012—Arrays characterised by the manufacturing method
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
  • C08J2343/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing boron, silicon, phosphorus, selenium, tellurium or a metal; Derivatives of such polymers
  • C08J2343/04—Homopolymers or copolymers of monomers containing silicon
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
  • C08J2383/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen, or carbon only; Derivatives of such polymers
  • C08J2383/04—Polysiloxanes

Definitions

• the present invention is directed to the surface treatment of silicone hydrogel contact lenses.
• the present invention is directed to a method of modifying the surface of a contact lens to increase its wettability and to decrease its susceptibility to protein and lipid deposition during use.
• the surface treatment results in a silicate- containing surface film or coating having a mosaic pattern of raised plates surrounded by receding spaces or fissures when viewing a 50X50 micron square AFM image of the surface, in which (i) the peak-to-valley distances of the fissures are on average between about 100 and 500 angstroms, (ii) the plate coverage is on average between about 40% to 99%, and (iii) the nitrogen elemental analysis is about 6.0 to 10.0 percent, which nitrogen has been enriched at least 10 percent relative to the pre-plasma treated lens surface, as determined by XPS analysis within a predetermined depth.
• Non-hydrogels do not absorb appreciable amounts of water, whereas hydrogels can absorb and retain water in an equilibrium state. Regardless of their water content, both non-hydrogel and hydrogel silicone contact lenses tend to have relatively hydrophobic, non-wettable surfaces.
• Silicone lenses have been subjected to plasma surface treatment to improve their surface properties, e.g., surfaces have been rendered more hydrophilic, deposit resistant, scratch resistant, or otherwise modified.
• plasma surface treatments include subjecting contact lens surfaces to a plasma comprising an inert gas or oxygen (see, for example, U.S. Patent Nos. 4,055,378; 4,122,942; and 4,214,014); various hydrocarbon monomers (see, for example, U.S. Patent No. 4,143,949); and combinations of oxidizing agents and hydrocarbons such as water and ethanol (see, for example, WO 95/04609 and U.S. Patent No 4,632,844).
• a process for providing a barrier coating on a silicone or polyurethane lens by subjecting the lens to an electrical glow discharge (plasma) process conducted by first subjecting the lens to a hydrocarbon atmosphere followed by subjecting the lens to oxygen during flow discharge, thereby increasing the hydrophilicity of the lens surface.
• plasma electrical glow discharge
• -2- will generally allow the use of a silicone hydrogel contact lens in the human eye for extended period of time.
• a silicone hydrogel lens for extended wear it would be highly desirable to provide a contact lens with a surface that is also highly permeable to oxygen and water.
• Such a surface treated lens would be comfortable to wear in actual use and would allow for the extended wear of the lens without irritation or other adverse effects to the cornea. It would be desirable if such a surface treated lens were a commercially viable product capable of economic manufacture.
• the present invention is directed to a silicone hydrogel lens with a silicate- containing surface film having a mosaic pattern of projecting plates surrounded by receding spaces or fissures when viewing a 50-by-50 micron square AFM (Atomic Force Microscopy) image in which (i) the average peak-to-valley distance (or average depth) of the fissures is between about 100 and 500 angstroms, (ii) the plate coverage is on average about 40% to 99%, and (iii) the nitrogen elemental analysis is about 6.0 to 10.0 percent and is at least 10 percent enriched in nitrogen relative to the pre-plasma treated lens surface, as determined by XPS analysis within a predetermined depth.
• AFM Average Force Microscopy
• the present invention is also directed to a method of modifying the surface of a contact lens to increase its wettability and to increase its resistance to the formation of deposits during wear.
• the surface film can be made by oxidative plasma treatment of the lens under suitable plasma conditions followed by hydration and autoclaving.
• FIG. 1 is a flow chart of a manufacturing process for making a lens having a lens coating according to the present invention.
• FIG. 2 is an Atomic Force Microscopy (AFM) topographical image (50x50 microns) showing a plasma-treated lens before further processing by extraction, hydration and sterilization according to the present invention.
• AFM Atomic Force Microscopy
• FIG. 3 is an Atomic Force Microscopy (AFM) topographical image (50x50 square microns) showing, for comparison, a hydrated and autoclaved plasma-treated lens (fully processed) after a time period of only 4 minutes, otherwise processed comparably to the lens in FIG. 3, showing a relatively smooth surface with barely visable plates and about 20 percent surface coverage.
• AFM Atomic Force Microscopy
• FIG. 4 is an Atomic Force Microscopy (AFM) topographical image (50x50 microns) showing a plasma-treated lens according to the present invention that has been extracted with isopropanol and prior to autoclaving, showing about 50 percent surface coverage.
• AFM Atomic Force Microscopy
• FIG. 5 is an Atomic Force Microscopy (AFM) topographical image (50x50 microns) showing a hydrated and autoclaved plasma-treated lens (fully processed) according to the present invention, after a time period of 8 minutes per side according to the conditions of Example 1, showing about 95% surface coverage. All AFM images are on dried samples.
• AFM Atomic Force Microscopy
• the present invention is directed to a silicone hydrogel contact lens having a silicate-containing coating and a method of manufacturing the same, which coating improves the hydrophilicity and lipid/protein resistance of the lens.
• the silicate-containing coating allows a lens that could otherwise not be comfortably worn in the eye to be worn in the eye for an extended period of time, for more than 24 hours at a time.
• silicone hydrogel lenses may be plasma treated in an unhydrated state, such lenses, unlike their non-hydrogel counterparts, are subsequently swollen by solvent extraction and hydration, which can cause the dimensions of the lens to substantially change after coating.
• hydration may cause the lens to swell from about 10 to more than about 20 percent or more, depending upon the ultimate water content of the lens.
• the subsequent autoclaving of the hydrated lens a common form of sterilizing lenses during the manufacture of packaged lenses, has also been found to substantially affect the plasma modified lens surface.
• the present invention is directed to a surface-modified silicone hydrogel lens having a silicate-containing coating that exhibits desirable coating characteristics, even after the lens has been extracted, hydrated, and autoclaved.
• the surface of a silicone hydrogel contact lens comprising, in bulk formula, 5 to 50 percent by weight of one or more silicone macromonomers, 5 to 75 percent by weight of one or more polysiloxanylalkyl (meth)acrylic monomers, and 10 to 50 percent by weight of a lactam-containing monomer is provided with a silicate- containing coating that displays a mosaic-like pattern of relatively flat plates surrounded and separated by relatively narrow spaces or fissures wherein (i) the plates provide a surface coverage on average of between about 40 percent to 99 percent, (ii) the fissures have a peak-to-valley distance on average of between 100 and 500 angstroms, and (iii) the nitrogen elemental analysis is about 6.0 to 10.0 percent and is at least 10 percent enriched in nitrogen relative to the pre-plasma treated lens surface, as determined by XPS analysis within a predetermined depth.
• Hydrogels in general are a well known class of materials which comprise hydrated, cross-linked polymeric systems containing water in an equilibrium state. Silicone hydrogels generally have a water content greater than about 5 weight percent and more commonly between about 10 to about 80 weight percent. Such materials are usually prepared by polymerizing a mixture containing at least one silicone-containing monomer and at least one hydrophilic monomer. Typically, either the silicone- containing monomer or the hydrophilic monomer functions as a crosshnking agent (a crosslinker being defined as a monomer having multiple polymerizable functionalities) or a separate crosslinker may be employed.
• a crosshnking agent a crosslinker being defined as a monomer having multiple polymerizable functionalities
• Examples of applicable silicon-containing monomeric units include bulky polysiloxanylalkyl (meth)acrylic monomers.
• An example of bulky polysiloxanylalkyl (meth)acrylic monomers are represented by the following Formula I:
• X denotes -O- or -NR-; each R, 8 independently denotes hydrogen or methyl; each R, 9 independently denotes a lower alkyl radical, phenyl radical or a group represented by
• each R 19 independently denotes a lower alkyl or phenyl radical; and h is 1 to 10.
• Some preferred bulky monomers are methacryloxypropyl tris(trimethyl- siloxy)silane or tris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred to as TRIS, and tris(trimethylsiloxy)silylpropyl vinyl carbamate, sometimes referred to as TRIS-VC.
• silicon-containing monomers includes silicone- containing vinyl carbonate or vinyl carbamate monomers such as: l,3-bis[4- vinyloxycarbonyloxy)but-l-yl]tetramethyl-disiloxane; 3-(trimethylsilyl)propyl vinyl carbonate; 3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane]; 3-[tris(tri- methylsiloxy)silyl] propyl vinyl carbamate; 3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate; 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate; t-butyldimethyl- siloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate; and trimethylsilylmethyl vinyl carbonate.
• silicone- containing vinyl carbonate or vinyl carbamate monomers such as: l,3-bis[4- vinyloxycarbonyloxy
• Y' denotes -O-, -S- or -NH-;
• RS I denotes a silicone-containing organic radical
• R 20 denotes hydrogen or methyl
• d is 1 , 2, 3 or 4
• q is 0 or 1.
• Suitable silicone-containing organic radicals R ⁇ 1 include the following:
• R- denotes an alkyl radical or a fluoroalkyl radical having 1 to 6 carbon atoms; e is 1 to 200; n' is 1, 2, 3 or 4; and m* is 0, 1, 2, 3, 4 or 5.
• silicon-containing monomers includes polyurethane- polysiloxane macromonomers (also sometimes referred to as prepolymers), which may have hard-soft-hard blocks like traditional urethane elastomers. They may be end-capped with a hydrophilic monomer such as HEMA.
• silicone urethanes are disclosed in a variety or publications, including Lai, Yu-Chin, "The Role of Bulky Polysiloxanylalkyl Methacryates in Polyurethane-Polysiloxane Hydrogels, " Journal of Applied Polymer Science, Vol. 60, 1193-1199 (1996). PCT Published Application No.
• WO 96/31792 discloses examples of such monomers, which disclosure is hereby incorporated by reference in its entirety.
• Further examples of silicone urethane monomers are represented by Formulae IV and V: (IV) E(*D*A*D*G) a *D*A*D*E'; or
• D denotes an alkyl diradical, an alkyl cycloalkyl diradical, a cycloalkyl diradical, an aryl diradical or an alkylaryl diradical having 6 to 30 carbon atoms;
• G denotes an alkyl diradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, an aryl diradical or an alkylaryl diradical having 1 to 40 carbon atoms and which may contain ether, thio or amine linkages in the main chain;
• * denotes a urethane or ureido linkage; a is at least 1 ;
• A denotes a divalent polymeric radical of Formula VI:
• each R-. independently denotes an alkyl or fluoro-substituted alkyl group having 1 to 10 carbon atoms which may contain ether linkages between carbon atoms; m' is at least 1 ; and p is a number which provides a moiety weight of 400 to 10,000; each of E and E' independently denotes a polymerizable unsaturated organic radical represented by Formula VII:
• R 23 is hydrogen or methyl
• R 24 is hydrogen, an alkyl radical having 1 to 6 carbon atoms, or a -CO-Y-R 26 radical wherein Y is -O-, -S- or -NH-;
• R 25 is a divalent alkylene radical having 1 to 10 carbon atoms
• R 26 is a alkyl radical having 1 to 12 carbon atoms
• X denotes -CO- or -OCO-
• Z denotes -O- or -NH-
• Ar denotes an aromatic radical having 6 to 30 carbon atoms; w is 0 to 6; x is 0 or 1 ; y is 0 or 1 ; and z is 0 or 1.
• m is at least 1 and is preferably 3 or 4
• a is at least 1 and preferably is 1
• p is a number which provides a moiety weight of 400 to 10,000 and is preferably at least 30
• R 27 is a diradical of a diisocyanate after removal of the isocyanate group, such as the diradical of isophorone diisocyanate
• each E" is a group represented by:
• the silicone hydrogel material comprises (in bulk, that is, in the monomer mixture that is copolymerized) 5 to 50 percent, preferably 10 to 25, by weight of one or more silicone macromonomers, 5 to 75 percent, preferably 30 to 60 percent, by weight of one or more polysiloxanylalkyl (meth)acrylic monomers, and 10 to 50 percent, preferably 20 to 40 percent, by weight of a hydrophilic monomer that is a lactam-containing monomer, for example, a vinyl lactam such as N-vinyl pyrrolidone, wherein the percentages are based on the hydrogel polymer material. Lactam-containing monomers are known to have a relatively low critical surface tension among hydrophilic monomers.
• the relatively low critical surface tension of N-vinyl pyrrolidone and other lactams (such that the difference from the silane monomers and macromers is relatively less) is believed to result in a controlled amount of layering such that a silicon enriched layer forms at the surface of the lens following molding, and a nitrogen enriched layer forms at a sufficiently close distance from the surface such that the nitrogen enriched layer becomes exposed following the Assuring and autoclaving of the lens surface during manufacture.
• the exposed nitrogen enriched layer is advantageous, not only for because of its hydrophilc nature which aids comfort, but because the nitrogen enrichment is believed to contribute to improved interfacial adhesion, and hence permanence, of the silicate- containing coating.
• Additional hydrophilic monomers in lesser proportions, for use in silicone hydrogels, which however, have a significantly higher critical surface tension, include: unsaturated carboxylic acids, such as methacrylic and acrylic acids; acrylic substituted alcohols, such as 2-hydroxyethylmethacrylate and 2-hydroxyethylacrylate and acrylamides, such as methacrylamide and N,N-dimethylacrylamide, vinyl carbonate or vinyl carbamate monomers such as disclosed in U.S. Patent Nos. 5,070,215, and oxazolone monomers such as disclosed in U.S. Patent No. 4,910,277.
• Other hydrophilic monomers will be apparent to one skilled in the art.
• the silicone macromonomer is a poly(organosiloxane) capped with an unsaturated group at two or more ends of the molecule.
• U.S. Patent No. 4,153,641 to Deichert et al. discloses additional unsaturated groups, including acryloxy or methacryloxy.
• the silane macromonomer is a silicon-containing vinyl carbonate or vinyl carbamate or a polyurethane-polysiloxane having one or more hard-soft-hard blocks and end-capped with a hydrophilic monomer.
• the lens material used in the present invention is non-fluorinated or has relatively little fluorine atoms.
• fluorination of certain monomers used in the formation of silicone hydrogels has been indicated to reduce the accumulation of deposits on contact lenses made therefrom, highly fluorinated materials, because of their particular chemical nature, cannot be used to produce the silicate-containing coatings according to the present invention.
• the present invention is also not applicable to fumarate siloxane hydrogel compositions according to US Patent No. 5,420,324.
• the surface silicon content of fumaride siloxane lenses is too high for the formation of a sufficiently flexible silicate material, so that the silicate surface formed by oxidative plasma treatment is too glasslike, delaminating during subsequent processing.
• the silicon content of the surface layer being treated may be either a result of the bulk chemistry of the composition, including its hydrophobic and hydrophilic portions, and/or a result of a surface layering phenomenon resulting in a relative enrichment of layers with respect to different monomers or elements.
• the desired coating in a fully processed coating according to the present invention, has sufficient silicate content to provide the desired surface properties, such as wettability and deposition resistance, and sufficient polymer content to allow sufficient flexibility during swelling and sufficient interfacial cohesion during heat sterilization to prevent delamination.
• the relative balance, in the coating, of hydrophobic and hydrophilic portions may also affect the coating's resistance to delamination during thermal and hydrodynamic expansion or stress.
• the hydrodynamic expansion of hydrogels in water is a function of the type and amount of the hydrophilic polymer content; and the thermal expansion is a
• the second may decrease, or vice versa.
• the chemistry of the silicate-containing coating or film in the final product is not completely made of silicate and some of the original material may remain in modified form.
• the coating formed by plasma treatment the original polymeric character of the material is changed to a more glass-like, hard material.
• the lens can be treated under two widely diverse plasma set of conditions, a first "low and slow” plasma treatment and a second "hot and fast” plasma treatment. If following the steps of plasma treatment, hydration, and heat sterilization (so-called “full processing"), a silicate coating can be obtained, then some further adjustment of the process conditions should be able to achieve a lens coating having surface characteristics according to the present invention.
• a "low and slow” surface treatment tends to be relatively more effective for a relatively higher silicon- containing lens; a "hot and fast” surface treatment is relatively more effective for a relatively lower silicon-containing lens.
• low and slow surface treatment is meant relatively lower time, higher pressure, and lower wattage, conditions designed to relatively minimize disruption of covalent bonds while modifying the substrate, thereby leaving more polymer at the coating interface with the lens material.
• Exemplary "low and slow” conditions for plasma treatment are 100 watts at 0.3 to 0.6 torr, 1-2 minutes per side, with 100 to 300 seem (standard cubic centimeters per minute) in an air/water/peroxide atmosphere (air bubbled through 8% hydrogen peroxide solution in HPLC grade water).
• hot and fast treatment is meant relatively higher wattage, lower pressure, and longer time, conditions designed to relatively maximize surface modification.
• Exemplary "hot and fast" conditions for plasma treatment are 400 watts at 0.1 to 0.4 torr, 10 minutes per side, with 200 to 500 seem in the above-indicated atmosphere.
• the existence of a silicate- containing coating can be evidenced by a recognizable or statistically significant change in the surface roughness (RMS), a visual change in the surface morphology as evidenced by AFM, such as the formation of surface plates, or by a statistically significant
• a preferred test for the formation of a coating is 1 to 5% change in oxygen content, within a 95% confidence level.
• any silicate coating in the fully processed lens can be formed by either "low and slow" treatment conditions or "hot and fast” treatment conditions, then it is generally possible to obtain a coating according to the present invention by subsequent process adjustments, without undue experimentation, as will be understood by the person skilled in the art. It is noted that the formation of a silicate coating merely following plasma treatment is not the test for the applicability, since subsequent delamination during heat sterilization may occur such that no coating would be apparent in the fully processed lens.
• Contact lenses according to the present invention can be manufactured, employing various conventional techniques, to yield a shaped article having the desired posterior and anterior lens surfaces.
• Spincasting methods are disclosed in US Patent Nos. 3,408,429 and 3,660,545; preferred static casting methods are disclosed in US Patent Nos. 4,113,224 and 4,197,266.
• Curing of the monomeric mixture is often followed by a machining operation in order to provide a contact lens having a desired final configuration.
• US Patent No. 4,555,732 discloses a process in which an excess of a monomeric mixture is cured by spincasting in a mold to form a shaped article having an anterior lens surface and a relatively large thickness.
• the posterior surface of the cured spincast article is subsequently lathe cut to provide a contact lens having the desired thickness and posterior lens surface. Further machining operations may follow the lathe cutting of the lens surface, for example, edge finishing operations.
• FIG. 1 illustrates a series of manufacturing process steps for static casting of lenses, wherein the first step is tooling (1) whereby, based on a given lens design, metal tools are fabricated by traditional machining and polishing operations. These metal tools are then used in injection or compression molding to produce a plurality of thermoplastic molds which in turn are used to cast the desired lenses from polymerizable compositions. Thus, a set of metal tools can yield a large number of thermoplastic molds.
• thermoplastic molds may be disposed after forming a single lens.
• the metal molds fabricated during tooling ( 1 ) is then used for anterior molding (2) and posterior molding (3) in order to produce, respectively, an anterior mold section for forming the desired anterior lens surface and a posterior mold section for forming the desired posterior lens surface.
• a monomer mixture (5) is injected into the anterior mold section, and the posterior mold section is pressed down and clamped at a given pressure to form the desired lens shape.
• the clamped molds may be cured by exposure to UV light or other energy source for a certain period of time, preferably by conveying the molds through a curing chamber, after which the clamps are removed.
• Suitable organic diluents include, for example, monohydric alcohols, with C 6 -C 10 straight-chained aliphatic monohydric alcohols such as n-hexanol and n-nonanol being especially preferred; diols such as ethylene glycol; polyols such as glycerin; ethers such as diethylene glycol monoethyl ether; ketones such as methyl ethyl ketone; esters such as methyl enanthate; and hydrocarbons such as toluene.
• the organic diluent is sufficiently volatile to facilitate its removal from a cured article by evaporation at or near ambient pressure.
• the diluent is included at 5 to 60% by weight of the monomeric mixture, with 10 to 50% by weight being especially preferred.
• the cured lens is then subjected to solvent removal (6), which can be accomplished by evaporation at or near ambient pressure or under vacuum.
• solvent removal (6) can be accomplished by evaporation at or near ambient pressure or under vacuum.
• An elevated temperature can be employed to shorten the time necessary to evaporate the diluent.
• temperature and pressure conditions for the solvent removal step will vary depending on such factors as the volatility of the diluent and the specific monomeric components, as can be readily determined by one skilled in the art.
• the temperature employed in the removal step is preferably at least 50°C, for example, 60 to 80 °C.
• a series of heating cycles in a linear oven under inert gas or vacuum may be used to optimize the efficiency of the solvent removal.
• the cured article after the diluent removal step should contain no more than 20% by weight of diluent, preferably no more than 5% by weight or less.
• the lens is next subjected to mold release and optional machining operations (7) according to the embodiment of FIG. 1.
• the machining step includes, for example, buffing or polishing a lens edge and/or surface.
• machining processes may be performed before or after the article is released from a mold part.
• the lens is dry released from the mold by employing vacuum tweezers to lift the lens from the mold, after which the lens is transferred by means of mechanical tweezers to a second set of vacuum tweezers and placed against a rotating surface to smooth the surface or edges. The lens may then be turned over in order to machine the other side of the lens.
• the lens is subjected to surface treatment (8), preferably by means of oxidative RF plasma treatment of the lens surface employing an oxygen-containing gas.
• Plasma treatment involves passing an electrical discharge through a gas at low pressure.
• the electrical discharge is usually at radio frequency (typically, 13.56 MHz), although microwave and other frequencies can be used. This electrical discharge is absorbed by atoms and molecules in their gas state, thus forming a plasma which interacts with the surface of the contact lens.
• an oxidizing plasma e.g., employing O, (oxygen gas), water, hydrogen peroxide, air, etc., or mixtures thereof, has been used to etch the surface of the lens, creating radicals and oxidized functional groups.
• O, (oxygen gas) oxygen gas
• water hydrogen peroxide
• air etc.
• oxidized functional groups such as oxygen and hydrogen.
• Such oxidation is known to render the surface of a silicone lens more hydrophilic; however, the bulk properties of the silicone materials may remain apparent at the surface of the lens or may become apparent after a relatively short period of use. For example, when the oxidation is relatively superficial, the silicone chains adjacent the lens surface are capable of migrating and/or
• the plasma conditions of the present invention are adjusted and set to obtain the desired combination of ablation and oxidation of the surface material, based on careful quality control of the resulting coating.
• a relatively thick coating, a permanent barrier between the underlying silicone materials and the outer lens surface, is thereby achieved in the final product.
• a plasma for the surface modification of the lens is initiated by a low energy discharge. Collisions between energetic free electrons present in the plasma cause the formation of ions, excited molecules, and free radicals. Such species, once formed, can react with themselves in the gas phase as well as with further ground-state molecules.
• the plasma treatment may be understood as an energy dependent process involving energetic gas molecules. For chemical reactions to take place at the surface of the lens, one needs the required species (element or molecule) in terms of charge state and particle energy. Radio frequency plasmas generally produce a distribution of energetic species. Typically, the "particle energy" refers to the average of the so-called Boltzman-style distribution of energy for the energetic species.
• the electron energy distribution can be related by the ratio of the electric field strength sustaining the plasma to the discharge pressure (E/p).
• the plasma power density P is a function of the wattage, pressure, flow rates of gases, etc., as will be appreciated by the skilled artisan.
• Background information on plasma technology include the following: A. T. Bell, Proc. Intl. Conf. Phenom. Ioniz. Gases, "Chemical Reaction in Nonequilibrium Plasmas", 19-33 (1977); J. M. Tibbitt, R. Jensen, A. T. Bell, M. Shen, Macromolecules, "A Model for the Kinetics of Plasma Polymerization", 3_, 648- 653 (1977); J.
• the rate generally decreases as the pressure is increased.
• E/p the ratio of the electric field strength sustaining the plasma to the gas pressure
• the decrease in electron energy in turn causes a reduction in the rate coefficient of all electron-molecule collision processes.
• a further consequence of an increase in pressure is a decrease in electron density. Providing that the pressure is held constant, there should be a linear relationship between electron density and power.
• contact lenses are surface treated by placing them, in their unhydrated state, within an electric glow discharge reaction vessel (e.g., a vacuum chamber).
• an electric glow discharge reaction vessel e.g., a vacuum chamber
• the lenses may be supported within the vessel on an aluminum tray (which acts as an electrode) or with other support devices designed to adjust the position of the lenses.
• the use of a specialized support devices which permit the surface treatment of both sides of a lens are known in the art and may be used in the present invention.
• the gas employed in the plasma treatment comprises an oxidizing media such as, for example, air, water, peroxide, O 2 (oxygen gas), or combinations thereof, at a electric discharge frequency of, for example, 13.56 MHz, suitably between about 100-1000 watts, preferably 200 to 800 watts, more preferably 300 to 500 watts, at a pressure of about 0.1- 1.0 Torr.
• the plasma treatment time is greater than 4 minutes per side, preferably at least about 5 minutes per side, more preferably about 6 to 60 minutes per side, most preferably about 8 to 30 minutes per side for effective but efficient manufacture. It is preferred that a relatively "strong" oxidizing plasma is utilized in this initial oxidation, e.g. ambient air drawn through a 3 to 30% by weight, preferably 4 to 15%), more preferably 5 to 10%) hydrogen peroxide solution, preferably at a flow rate of 50 to 500 seem, more preferably 100 to 300 seem.
• a relatively "strong" oxidizing plasma is utilized in this initial oxidation, e.g
• the postplasma coating thickness should be greater than 1000 angstroms, since substantial thickness will be lost during subsequent processing. Following hydration and autoclaving, as further discussed below, the surface becomes fissured and the thickness may be reduced more than 50 percent, even as much as 90 percent or more, from the initial coating thickness.
• the process parameters may need to be adjusted in order to obtain a combination of ablation and glass formation that results in the desired coating as subjected after being subjected to further processing steps.
• the thickness of the coating is sensitive to plasma flow rate and chamber temperature. Higher flow rates tend to cause more ablation; lower pressures tend to produce thicker coatings out of the plasma chamber. However, higher temperatures may tend to result in a surface that is less glassy and less cohesive.
• the optimal variables for obtaining the desired or optimal coating may require some adjustment. If one parameter is adjusted, a compensatory adjustment of one or more other parameters may be appropriate, so that some routine trial and error experiments and iterations thereof may be necessary in order to achieved the coating according to the present invention.
• adjustment of process parameters in light of the present disclosure and the state of the art in plasma treatment, should not involve undue experimentation. As indicated above, general relationships among process parameters are known by the skilled artisan, and the art of plasma treatment has become well developed in recent years. The Examples below provide the Applicants' best mode for forming the coating on a silicone hydrogel lens.
• the lens may be subjected to extraction (9) to remove residuals in the lenses.
• extraction 9
• some of the monomer mix is not fully polymerized.
• the incompletely polymerized material from the polymerization process may affect optical clarity or may be harmful to the eye.
• Residual material may include solvents not entirely removed by the previous solvent removal operation, unreacted monomers from
• the lens is subjected to hydration (10) in which the lens is fully hydrated with water, buffered saline, or the like.
• the coating remains intact and bound to the lens, providing a durable, hydrophilic coating which has been found to be resistant to delamination.
• the lens may undergo cosmetic inspection (11) wherein trained inspectors inspect the contact lenses for clarity and the absence of defects such as holes, particles, bubbles, nicks, tears. Inspection is preferably at 10X magnification.
• the lens is ready for packaging (12), whether in a vial, plastic blister package, or other container for maintaining the lens in a sterile condition for the consumer.
• packaging (12) whether in a vial, plastic blister package, or other container for maintaining the lens in a sterile condition for the consumer.
• the packaged lens is subjected to sterilization (13), which sterilization may be accomplished in a conventional autoclave, preferably under an air pressurization sterilization cycle, sometime referred to as an air-steam mixture cycle, as will be appreciated by the skilled artisan.
• sterilization may be accomplished in a conventional autoclave, preferably under an air pressurization sterilization cycle, sometime referred to as an air-steam mixture cycle, as will be appreciated by the skilled artisan.
• sterilization may be accomplished in a conventional autoclave, preferably
• -20- autoclaving is at 100° C to 200° C for a period of 10 to 120 minutes. Following sterilization, the lens dimension of the sterilized lenses ir ⁇ ay be checked prior to storage.
• the silicate-containing coating produced by plasma treatment has been modified to its final form, in which the coating displays a mosaic pattern of projecting plates surrounded by receding fissures, akin in appearance to closely spaced islands surrounding by rivers.
• the peak-to-valley distances (or depth) of the fissures is on average between about 100 and 500 angstroms
• the plate coverage (or surface coverage) is on average between about 40% and 99%
• the nitrogen elemental analysis is about 6.0 to 10.0 percent and is at least 10 percent enriched relative to the pre-plasma treated lens surface, as determined by XPS analysis within a predetermined depth.
• the depth of the fissures can be considered to be a measurement of the "coating thickness," wherein the fissures expose the underlying hydrogel material under the silicate-containing, glass-like coating.
• the peak-to-valley distances of the fissures is on average between 150 and 200 angstroms and preferably the plate coverage is on average about 50 %> to 99 percent, more preferably 60 to 99%>.
• the nitrogen elemental analysis is about 7.0 to 9.0 percent which has been enriched at least about 20 percent relative to the pre-plasma treated lens surface, more preferably greater than about 7.5 percent nitrogen and greater than about 25 %> nitrogen enrichment, according to XPS measurements the procedure of which is described in the Examples below.
• on average is meant a statistic average of measurements of controlled lots of lenses taken during commercial manufacture, based on average measurements of each lens in the optical zone.
• the average for each lens is calculated based on the evaluation of three 50x50 square micron images per side of the each lens, as in the examples below.
• controlled manufacture or “controlled process” is meant that the manufactured product is consistently produced and subject to quality control so that the average values are within a preselected range, or within a preselected range of specifications, with respect to fissure depth and plate coverage.
• at least 70%, more preferably at least 80%>, most preferably at least 90%> of the manufactured lenses, with a 95%> confidence level should
• the average value, for surface coverage and coating thickness, of the manufactured lenses should be within the claimed ranges within a 90% confidence level, more preferably within a 95%> confidence level.
• This example discloses a representative silicone hydrogel lens material used in the following Examples.
• the formulation for the material is provided in Table 1 below.
• V 2 D 25 a silicone-containing vinyl carbonate as previously described in US Patent No. 5,534,604.
• This Example illustrates a process for the surface modification of a contact lens according to the present invention.
• Silicone hydrogel lenses made of the formulation of Example 1 above were cast molded from polypropylene molds. Under an inert nitrogen atmosphere, 45- ⁇ l of the formulation was injected onto a clean polypropylene concave mold half and covered with the complementary polypropylene convex mold half. The mold halves were compressed at a pressure of 70 psi and the mixture was cured for about 15 minutes in the presence of UV light (6-11 mW/cm 2 as measured by a Spectronic UV meter). The mold was exposed to UV light for about 5 additional minutes.
• the top mold half was removed and the lenses were maintained at 60°C for 3 hours in a forced air oven to remove n-hexanol. Subsequently, the lens edges were ball buffed for 10 seconds at 2300 rpm with a force of 60 g.
• the lenses were then plasma treated as follows: The lenses were placed concave side up on an aluminum coated tray and the tray placed into a plasma treatment chamber. The atmosphere was produced by passing air at 400sccm into the chamber through an 8% peroxide solution, resulting in an Air/H 2 O H 2 O 2 gas mixture. The lenses were plasma treated for a period of 8 minutes (350 watts, 0.5 Torr). The chamber was then backfilled to ambient pressure. The tray was then removed from the chamber, the lenses flipped over, and the procedure repeated to plasma treat the other side of the lenses.
• Lenses were analyzed directly from the plasma chamber and after full processing. Full processing included, following plasma treatment, extraction, hydration and autoclave sterilization. Extraction employed isopropanol at room temperature for 4 hours (during commercial manufacture a minimum of 48 hours following by extraction in water at about 85°C for 4 hours is preferred). The lenses were then immersed in buffered saline for hydration. Autoclaving was carried out with the lenses, within vials, immersed in an aqueous packaging solution.
• the plasma chamber was a direct current DC RFGD chamber manufactured by Branson GaSonics Division (Model 7104). This chamber was a cold equilibrium planar configuration which had a maximum power of 500 watts. All lenses were prepumped to 0.01 Torr prior to any plasma treatment from residual air in the chamber. This process reduced the relative treatment level of the polymer by controlling gas pressure.
• the XPS data was acquired by a Physical Electronics [PHI] Model 5600 Spectrometer. To collect the data, the instrument's aluminum anode was operated at 300 watts, 15 kV, and 20 mA. The Al K ⁇ line was the excitation source monochromatized by a toroidal lens system. A 7 mm filament was utilized by the X-ray monochromator to focus the X-ray source which increases the need for charge dissipation through the use of a neutralizer. The base pressure of the instrument was 2.0 x 10-10 Torr while during operation it was 1.0 x 10-9 Torr. A hemispherical energy analyzer measures electron kinetic energy. The practical sampling depth of the instrument, with respect to carbon, at a sampling angle of 45°, is approximately 74 Angstroms. All elements were charge corrected to the CH X peak of carbon binding energy of 285.0 eV.
• Each of the plasma modified specimens were analyzed by XPS utilizing a low resolution survey spectra [0-1100 eV] to identify the elements present on the sample surface.
• the high resolution spectra were performed on those elements detected from the low resolution scans.
• the elemental composition was determined from the high resolution spectra.
• the atomic composition was calculated from the areas under the photoelectron peaks after sensitizing those areas with the instrumental transmission function and atomic cross sections for the orbital of interest. Since XPS does not detect the presence of hydrogen or helium, these elements will not be included in any calculation of atomic percentages.
• the atomic composition data has been outlined in Table 2.
• the survey spectra for the pre-plasma lenses of Experiments 1 to 3 contain photoelectron peaks indicative of oxygen, nitrogen, carbon, and silicon.
• the silicon 2p 3/2 peak position (102.4eV) indicates that the detected silicon on the surface originated from derivatives of silicone.
• the survey spectra for the post-plasma lenses of the Experiments 1 to 3 contain photo-electron peaks indicative of oxygen, nitrogen, carbon, silicon, and fluorine.
• the fluorine is a by-product of the plasma ablation of the Teflon runners which support the
• the silicon 2p 3 , 2 photoelectron peak position (103.7 eV) indicates that the detected silicon on the surface originated from silicates, verifying the presence of a coating.
• slight differences in the elemental analyses for different experiments may result from slight variations in the plasma processing parameters, location in the chamber, or as a result of inherent surface properties of the lenses of this particular lot.
• AFM Atomic Force Microscopy
• plate coverage The fraction of the lens surface that is covered by the coating is referred to as "plate coverage” or “surface coverage.” This measurement is sometimes easily made by looking at a histogram of the surface heights. However, when the coating is too thin, ( ⁇ 10 nm) the coverage is not attainable from the histogram. When this occurs, the AFM image in question is compared to previous AFM images of which the exact coverage is known. When this visual method is used, the coverage is estimated and correct to within ⁇ 10%.
• FIG. 2 is an Atomic Force Microscopy (AFM) topographical image showing a plasma-treated lens before further processing by hydration and autoclaving.
• the image shows a lens coating with a smooth surface (100% surface coverage) very similar in appearance to the surface before plasma treatment. This is because most plasma coatings are conformal to the original surface. As evident, the surface is not perfectly smooth. The surfaces show some fine multidirectional scratches due to tooling marks.
• AFM Atomic Force Microscopy
• FIG. 3 for comparison to a lens surface according to the present invention, is an Atomic Force Microscopy (AFM) photograph showing an autoclaved plasma-treated lens (fully processed) after a plasma treatment time period of only 4 minutes per side but otherwise comparable to the process conditions of this Example.
• the coating thickness is an Atomic Force Microscopy (AFM) photograph showing an autoclaved plasma-treated lens (fully processed) after a plasma treatment time period of only 4 minutes per side but otherwise comparable to the process conditions of this Example.
• FIG. 4 is an Atomic Force Microscopy (AFM) image of an plasma-treated lens following extraction with isopropanol.
• the lens thickness is about 100 nm (which will be reduced during subsequent autoclaving), and the surface coverage is about 50 percent. Since the AFM images are in the dry state, the surface coverage of the extracted and fully processed lenses are comparable.
• AFM Atomic Force Microscopy
• FIG. 5 is an Atomic Force Microscopy (AFM) topographical image (50x50 square microns) showing a hydrated and autoclaved plasma-treated lens (fully processed according to the present invention) after a time period of 8 minutes, showing distinct plates with excellent surface coverage.
• the coating thickness is about 10 +1-2 nm thick (100 angstroms) with about 95 percent surface coverage.
• the average depth of the fissures in the coating (also referred to as the "coating thickness") were directly measured using AFM software.
• the thickness of 3-5 islands (arbitrarily selected) in each picture is measured and averaged to yield an overall coating thickness for each image.
• the RMS roughness of the fully processed lens is less than about 50 nm, more preferably about 2 to about 25 nm, most preferably 5 to 20 nm.
• Silicon hydrogel lenses of the formulation in Example 1 above were plasma treated for a period of time of 4 minutes per side and used in a clinical study. Due to variance in the lens surface topography some of the lots showed a smooth surface without any evidence of plates when inspected employing surface imaging by Atomic Force Microscopy (AFM), in which a 50X50 micron square image was made of a typical
• the lenses used in the clinical study were sorted by degree of deposition based on information provided by practitioners involved in the study.
• the Grade Levels were from 0 to 4 corresponding to increasing levels of deposition via slit lamp analysis.
• the lenses were worn for 3 months with enzyme cleaning at the end of a week of wear and then disinfected with ReNu MPS solution overnight. In some cases, the lens was replaced before the 3 months due to specified reasons. In all other instances, the lens was worn for the entire study. After 3 months, all lenses were shipped (in a dry state) and stored in a refrigerator upon arrival.
• the standard protein solution utilized was BSA with a standard concentration range of 0 - 200 ⁇ g.
• the analytical protocol was as follows:
• Tubes are then placed in a water bath at 37° for 15 minutes. After incubation, the purple complex develops.
• GC Gas Chromatography
• a 2 ⁇ l amount from each tube is then injected into the GC.
• the syringe was cleaned 10-14 times with hexane between each run.
• the retention time of the lipids corresponds to chain length.
• C 8 - C, 2 , C 12 , C M and C l6 - C l8 come off at increasing intervals.
• the GC is a Capillary CG 30ft HPR1 column attached to an FID detector (mass), so mass can be read corresponding to the peaks (in ⁇ g).
• Numbers in bold represent the total number of patients with that Grade of deposition.
• the following table shows the distribution of the lots among the Grades of deposition demonstrating the relative susceptibility of lenses in particular lots to deposition.
• contact angle measurements were made of an untreated lens (before plasma treatment), a plasma treated lens (immediately after plasma treatment) and after fully processing (including hydration and heat sterilization).
• the contact angle was measured as follows.
• a platinum wire (Pt) was employed to minimize contamination.
• the Pt wire was pulled across a flame over a Bunsen burner until the wire reached a dull red (orange) glow, in order to ensure that the water (HPLC grade) employed in the test was exposed to a fresh, clean metal surface, free from contamination.
• About 2 microliters of water was transferred from its bottle to the wire, which process involved tipping of the bottle so that the maximum amount of wire was under the liquid.
• the water on the wire was transferred, without dragging along the surface, to a lens made from the material of Example 1. Once transferred, an NRL-100 Rhame-Hart Contact Angle Goniometer was
• the contact angle formed by the drop was measured on the right and on the left. Another drop of water was added to the first drop, and then the contact angles were recalculated for the left and right sides. All four measurements were averaged.
• the lens surface before treatment exhibited a water contact angle of about 90 dynes/cm. Following plasma treatment, the water contact angle was 0 dynes/cm. Following heat sterilization, the fully processed lens exhibited a contact angle of 72.4 +/- 2 dynes/cm. All measurements were on dry lenses.

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