WO1994011118A1 - Biocompatible, surface modified materials and method of making the same - Google Patents

Biocompatible, surface modified materials and method of making the same Download PDF

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Publication number
WO1994011118A1
WO1994011118A1 PCT/US1993/010695 US9310695W WO9411118A1 WO 1994011118 A1 WO1994011118 A1 WO 1994011118A1 US 9310695 W US9310695 W US 9310695W WO 9411118 A1 WO9411118 A1 WO 9411118A1
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WO
WIPO (PCT)
Prior art keywords
polymeric
biocompatible
radio frequency
substrate
substrate material
Prior art date
Application number
PCT/US1993/010695
Other languages
French (fr)
Inventor
Ihab Kamel
David B. Soll
Original Assignee
Drexel University
Ophthalmic Research Corporation
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Application filed by Drexel University, Ophthalmic Research Corporation filed Critical Drexel University
Priority to AU58453/94A priority Critical patent/AU5845394A/en
Priority to EP94904375A priority patent/EP0668798A4/en
Priority to JP6512237A priority patent/JPH08505295A/en
Publication of WO1994011118A1 publication Critical patent/WO1994011118A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/16Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16Intraocular lenses
    • A61F2/1613Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0076Chemical modification of the substrate
    • A61L33/0088Chemical modification of the substrate by grafting of a monomer onto the substrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/06Use of macromolecular materials
    • A61L33/08Polysaccharides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00Processes for applying liquids or other fluent materials
    • B05D1/62Plasma-deposition of organic layers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D3/00Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
    • B05D3/14Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by electrical means
    • B05D3/141Plasma treatment
    • B05D3/142Pretreatment
    • B05D3/144Pretreatment of polymeric substrates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C59/00Surface shaping of articles, e.g. embossing; Apparatus therefor
    • B29C59/14Surface shaping of articles, e.g. embossing; Apparatus therefor by plasma treatment
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12Chemical modification
    • C08J7/16Chemical modification with polymerisable compounds
    • C08J7/18Chemical modification with polymerisable compounds using wave energy or particle radiation
    • CCHEMISTRY; METALLURGY
    • C23COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23CCOATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C8/00Solid state diffusion of only non-metal elements into metallic material surfaces; Chemical surface treatment of metallic material by reaction of the surface with a reactive gas, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
    • C23C8/06Solid state diffusion of only non-metal elements into metallic material surfaces; Chemical surface treatment of metallic material by reaction of the surface with a reactive gas, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using gases
    • C23C8/36Solid state diffusion of only non-metal elements into metallic material surfaces; Chemical surface treatment of metallic material by reaction of the surface with a reactive gas, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using gases using ionised gases, e.g. ionitriding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/16Intraocular lenses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0077Special surfaces of prostheses, e.g. for improving ingrowth
    • A61F2002/009Special surfaces of prostheses, e.g. for improving ingrowth for hindering or preventing attachment of biological tissue
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29KINDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037Other properties
    • B29K2995/0056Biocompatible, e.g. biopolymers or bioelastomers

Definitions

  • the present invention relates to methods of permanently modifying the surface of materials by plasma-induced and, where desired, post-plasma reactions to produce biocompatible, surface modified materials.
  • the present invention relates to biocompatible, surface modified prostheses and, in particular, to a biocompatible, surface modified intraocular lens used in mammals.
  • Prosthetic devices or prostheses are commonly used in medical procedures to replace or augment defective organs in mammals and humans. Such prostheses are numerous and diverse in structure and application. Examples of pro ⁇ theses include artificial joints, valve replacements, artificial skin, vascular grafts, shunts, plates and contact and intraocular lenses.
  • Typical prosthetic materials include metals, ceramics, silicone rubbers, polyesters, polyurethanes and/or polysulfones.
  • Synthetic polymers such as polymethylmethacrylate (PMMA) , silicone elastomers and polymers of hydroxyethylmethacrylate (HEMA) , are preferred polymers for prosthetic use in general and contact lenses and intraocular lenses in particular.
  • PMMA has several beneficial characteristics for prosthetic use, including excellent light transmission capability, good optical clarity, resistance to fluid diffusion and jln vivo deterioration, ease in processing (injection molding or machining, for example) and ease in implantation.
  • machining process typically leaves circular lathe marks or grooves visible at even relatively low magnification. These machining marks render the lens unusable until the lens surface is smoothed, typically by a mechanical polishing process.
  • conventional polishing processes generally take several days to complete, have failure rates in excess of 30% and fail to produce a microscopically smooth surface.
  • the -surfaces of injection molded lenses do not show machine lathe marks. However, their surfaces are also not microscopically smooth and reflect the surface finish of the mold.
  • typical prosthetic devices comprise natural and/or synthetic materials which are highly irregular on the cellular level. These rough prostheses, especially those which are implanted, can cause tissue irritation, cell proliferation, edema and scarring.
  • posterior lens capsule opacification is a prevalent problem among those patients who have received intraocular lens implants comprising conventionally polished PMMA and other similar materials. Pseudophakic precipitates on the surfaces of an intraocular lens can be indicative of microscopic surface irregularities.
  • biocompatible modified surface should be resistant to deterioration over time and should have no adverse effects on contacting tissues and cells.
  • U.S. Patent No. 3,961,379 discloses a bioi plantable device manufactured from a cross-linked, swollen, hydrophilic polymer. These modified polymers must be solid and must be swellable by fluid swelling substances. Once swollen, the solid polymer is polymerized with a modifying substance by, for example, high energy particle radiation.
  • U.S. Patent No. 4,189,364 discloses hydrophilic polymers formed in situ by irradiating a mixture of hydroxyalkyl ethacrylate and a cross-linking agent.
  • This patent discloses a process for forming hydrophilic polymer articles or hydrophilic polymer coatings on other substrates, such as glass or plastic, by polymerizing a hydrophilic monomer system by high energy particulate irradiation, such as accelerated electrons or nuclear particles including neutrons, protons, alpha, beta and/or gamma particles.
  • U.S. Patent No. 2,999,056 also discloses that an unsaturated organic acid may be attached to a shaped polymeric structure by ionizing radiation.
  • Other methods of altering the surface of polymeric objects include exposing the surface of a polymeric article to low temperature plasma or an electrically charged gaseous atmosphere, followed by contacting the surface of the polymeric article with a surface modifying compound as described, for example, in U.S. Patent No. 4,344,981. This two-step method is generally called plasma-induced coating. Plasma induction has been described generally in U.S. Patent No. 4,328,257, Ya ⁇ uda, "Plasma for Modification of Polymers," J. Macromol. Sci. C. Chem..
  • Ionized vapor or a plasma discharge is typically created in a vacuum chamber in which the object to be modified is placed.
  • the plasma discharge conditions the surface of the object by creating free radicals and/or ions. It is known, for example, that exposing the surface of an object to a plasma discharge, such as an oxygen plasma, enhances the wettability or hydrophilicity of such a surface. However, such treatment is only temporary.
  • U.S. Patent Nos. 3,925,178; 3,944,709; 4,072,769; 4,096,315; 4,122,942; 4,123,308; 4,131,691; 4,137,365; 4,214,014 and 4,478,873 disclose examples of polymers whose surface characteristics have been modified by a plasma discharge.
  • Plasma discharge treatment may also be used to prepare an object for the attachment or grafting of a compound or material to the plasma discharge treated object.
  • a plasma discharge step may be used to condition the surface for grafting by creating free radicals to which a compound or material may be grafted.
  • Such compounds or materials are generally called surface modifiers. Knight, P. M. et al., in "Surface Modification of Intraocular Lenses to Reduce Corneal Endothelial Damage," Am. Intra-ocular Implants Soc. J.
  • hydrophilic monomers in particular, HEMA and vinyl pyrrolidone
  • HEMA hydrophilic monomers
  • vinyl pyrrolidone vinyl pyrrolidone
  • This patent discloses a soft, highly oxygen permeable, hydrophobic polymeric lens which has a surface coating of an ultra-thin, optically clear, permeable barrier.
  • the coating is the reaction product re ⁇ ulting from a glow discharge polymerization process conducted in a hydrocarbon or halogenated hydrocarbon gaseous atmosphere. While the plasma discharge process, itself, results in a hydrophilic surface, this patent discloses that subsequent exposure to a glow discharge atmosphere of oxygen or ambient oxygen yields a still more hydrophilic surface.
  • U.S. Patent 4,409,258 discloses a method for rendering contact lenses hydrophilic by bombarding the lens of PMMA or silicone, for example, with a positive ion beam generated by a plasma discharge, such as an oxygen plasma. The lens is thereafter hydrated, preferably at an elevated temperature.
  • U.S. Patent No. 4,143,949 discloses a discharge polymerization and coating process for making a hydrophilic contact lens from an oxygen permeable, hydrophobic polymer.
  • the hydrophobic lens is placed in a glow discharge apparatus containing an atmosphere comprising a polymerizable organic monomer, such as hydroxyalkyl acrylate or methacrylate, glycidyl methacrylate, propylene oxide or N-vinyl-2-pyrrolidone.
  • the glow discharge is used to polymerize the monomer onto the surface of the contact lens.
  • Other examples of surface treated polymeric objects include U.S. Patent Nos.
  • U.S. Patent No. 4,731,080 discloses a coated intraocular lens having a hydrophobic cros ⁇ -linked vinyl-containing silicone polymer placed on the lens surface in solution.
  • a biocompatible, surface modified material and a method for producing the same, wherein the surface of the substrate material is cleaned, and active species, such as ions and free radicals, are produced on the surface by a plasma treatment to enhance subsequent grafting of a polymeric biocompatible material to the substrate surface to provide a substantially permanent, smoot surface on a cellular level.
  • active species such as ions and free radicals
  • a method for grafting a polymeric biocompatible material to the surface of a substrat is disclosed in our U.S. Patent No. 5,080,924. By pretreatin the surface of the substrate material, the smoothness of the substrate and the grafted surface may be improved.
  • a method for permanently modifying a surface of a polymeric substrate material so that the substrate material develops a microscopically smooth, biocompatible surface.
  • the method comprises covalently grafting a biocompatible polymeric material to the surface of the substrate material by radio 7 -
  • the biocompatible polymeric material comprises substantially the same material as the polymeric substrate.
  • at least a portion of the surface of the polymeric substrate material is removed, such as by etching.
  • Another aspect of the present invention is another method for permanently modifying a surface of a substrate polymeric material.
  • the method comprises subjecting at least a portion of the surface of the polymeric substrate material to inert gas radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glass transition temperature (T g ) of the substrate material for a time sufficient to produce surface relaxation and a resulting microscopically smooth, biocompatible surface on the substrate material.
  • Yet another aspect of the present invention is a prostheses used in mammals which has a permanently modified microscopically smooth, biocompatible surface.
  • the prostheses comprises a polymeric material core and a biocompatible material grafted to the surface of a polymer core by radio frequency plasma treatment.
  • the biocompatible polymeric material comprises substantially the same material as the core.
  • the lens comprises a polymeric material lens body having a biocompatible polymeric material.
  • the biocompatible polymeric material is grafted to the surface of the lens body and comprises substantially the same material as the body.
  • a further aspect of the present invention is a method of manufacturing a prostheses to provide the prostheses with a microscopically smootlj, biocompatible surface without the use of mechanical polishing.
  • the method comprises covalently -grafting a polymeric biocompatible material to the - 8
  • the surface to be grafted may first be etched.
  • Fig. 1 is a graph of surface temperature of PMMA substrates as a function of time at various radio frequency power levels which shows the thermal annealing effect of argon plasma where the temperature of the substrate surface increases with plasma power and can be made to exceed the glass transition temperature, according to one embodiment of the present invention.
  • the substrate material used in accordance with the present invention is chosen dependent upon its intended use. For example, PMMA, HEMA and silicone are useful for making prosthetic devices intended for implantation or other applications in mammals.
  • any biocompatible organic polymer may be used as a substrate material, as well as certain ceramics.
  • the polymer comprise PMMA or a silicone elastomer.
  • At least a portion of the surface of the polymeric substrate material is removed to clean the substrate and produce active species on the polymer surface, such as ions and free radicals, which can be used for inducing a grafted reaction.
  • active species on the polymer surface such as ions and free radicals
  • the removal of the portion of the surface material is accomplished by inert gas etching.
  • the etching may be induced in a radio frequency (RF) plasma reactor, such as are well known to those of ordinary skill in the art.
  • RF radio frequency
  • the Branson Model 3003-1813 is one example of a suitable radio frequency gas plasma reactor which may be used to etch the surface of the polymeric substrate material.
  • RF radio frequency
  • the rate of material removal is influenced by the frequency or power of the gas plasma, the treatment time, the gas used in the plasma reactor, the gas pressure/concentration and the type of bond present on the treated substrate material surface, depending on the particular substrate material.
  • frequency is kept at 13.56 MHz, which is suitable for etching.
  • the etching process includes injecting a noble or ambient gas into the reactor to create ions which bombard the substrate creating active sites on the substrate .surface.
  • Nitrogen and ammonia gases are also believed to be useful in the radio frequency gas plasma reaction when nitrogenous compounds are desired.
  • the noble gas is argon, which create ⁇ active sites on the substrate surface but does not produce new chemical groups when applied to the substrate surface in a RF gas.plasma reactor.
  • a noble gas such as argon
  • Oxygen on the other hand, for example, tends to produce peroxides in such plasma-induced grafting reactions and is, therefore, generally less stable chemically.
  • suitable gases which may be used in the plasma reaction in accordance with the present invention.
  • the substrate surface to be etched is first cleaned with a mild soap solution, i.e., a 1% sodium decyl sulphate solution, and rinsed in deionized water to remove any contaminants that may be present from the manufacturing processes and subsequent handling.
  • the lens or other substrate is positioned in the radio frequency plasma reactor on a glas ⁇ or other suitable fixture.
  • the pressure in the reactor is reduced to less than about 0.05 to about 0.1 torr for about 5 to about 10 minutes.
  • Argon gas is introduced into the chamber at a pressure of about 8 to about 10 psi and the pressure within the reaction chamber is adjusted to about 0.3 to about 0.5 torr for about 5 to about 10 minute ⁇ to purge the chamber with the argon gas.
  • Radio frequency power was - 11
  • the substrate surface may be subjected to radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glass transition temperature (T g ) of the substrate material for a time sufficient to produce a microscopically smooth, biocompatible surface on the substrate material.
  • T g glass transition temperature
  • Fig. 1 is a graph of substrate surface temperature of PMMA substrates as a function of time at several power levels ranging from 30 to 150 watts.
  • the temperature of the substrate surface increases during plasma treatment. For example, at 150 watts of power, the temperature of the substrate climbs about 60°C after 10 minutes of plasma treatment. Where temperatures above the glass transition temperature are desired, relatively higher radiation power is preferred. For example, to reach a surface temperature of about 105°C, which is the glass transition temperature of PMMA, radiation power of about 120 to about 150 watts is preferred.
  • T g glass transition temperature
  • the method includes a step of covalently grafting a polymeric biocompatible material to the surface of the substrate material by radio frequency plasma treatment.
  • the biocompatible polymeric material is introduced in the monomer form and is selected from ethylenediamine, hexamethyldisiloxane, acrylic acid, diethylenetriamine, allylamine, hydroxyethylmethacrylate, methylmethacrylate and combinations thereof, for example.
  • Polymeric grafts of silicone, polypropylene, polyester, polytetrafluoroethylene, polyethylene terephthalate or polyurethane may be similarly formed on the surface of the substrate material by appropriate reaction.
  • the resulting biocompatible polymeric material is preferably grafted to the ⁇ ubstrate material in a relatively uniform thickness and texture along the surface of the substrate material.
  • the biocompatible polymeric material is present on the surface of the substrate material in a relatively uniform, small thickness to prevent 'interference with the optical clarity of the lens. More preferably, the biocompatible polymeric material is present in few molecular layers.
  • a surface modified substrate comprises a biocompatible polymeric material grafted to the surface of a substrate material with a biocompatible polymeric material thickness of about lOO ⁇ .
  • grafting of the biocompatible polymeric material according to the present invention is conducted using radio frequency pla ⁇ ma-induced grafting.
  • Other methods of grafting such as electron beam or ultra-violet (UV) radiation, are not suitable where it is desired to modify only the surface of th substrate material.
  • a prosthetic lens such as a contact lens or intraocular lens
  • modification should be confined to the surface of the lens to avoid affecting the optical properties of the lens.
  • Radio frequency plasma-induced grafting according to the present invention avoids structural modification below th outer-most surface layer, and generally results in more desirable optical properties'.
  • Such gas plasma-induced grafting may be conducted i a radio frequency gas plasma reactor such as that discussed above capable of generating a frequency of about 1 MHz to about 40 MHz.
  • the frequency generated by a typical commercia gas plasma reactor is 13.56 MHz, although one skilled in the art will recognize that higher and lower frequencies may be used to graft the biocompatible polymeric material to the surface of the substrate material in a radio frequency gas plasma reactor, depending on the substrate material and biocompatible polymeric material used, the relative ease or difficulty in preparing the surface of the substrate material for grafting, the relative ease or difficulty of vaporizing o polymerizing the biocompatible material, among other factors.
  • the length of time the biocompatible material in an induced plasma state should be allowed to react with the substrate material depends upon several factors, including th plasma or radiation power, the radio frequency, the flow concentration or pressure, the temperature and the desired thickness of the grafted material.
  • the radiation power is about 10 watts to about 200 watts, depending upon th biocompatible material.
  • the biocompatible material comprises silazane, hexamethyldisiloxane, MMA, NVP o AA
  • the radiation power is - 14 -
  • the radiation power is about 10 watts to about 200 watts.
  • the reactor power used and the duration during which such power is used should be low and/or short enough so as to not induce thermal circulation and melt the substrate surface.
  • the reaction conditions i.e., power and duration
  • the desired plasma radiation power should be used in accordance with the present invention.
  • the temperature in the plasma reaction should not b allowed to approach those temperatures which may structurally damage the substrate material or the biocompatible material.
  • High radiation power and any polymerization reaction i.e., polymerization which may occur when the grafting reaction occurs; e.g.: polymerization to polymethylmethacrylate
  • polymerization to polymethylmethacrylate tend to increase the temperature of the plasma reaction zone. It is desirable, therefore, to maintain the temperature in the plasma reaction below the temperature at which the substrate material and/or the graft material will be damaged, typically below about 60°-80°C.
  • the flow concentration or vapor pressure of the plasma reactants in the reactor chamber should be low enough so that the particular monomer of the biocompatible material vaporizes when introduced into the reactor.
  • the vapor pressure is about 0.1 torr to about 0.6 torr. More preferably, the vapor pressure is about 0.4 torr.
  • the plasma reaction is preferably conducted for a period of time of about 1 minute to about 60 minutes. ' More preferably, the plasma reaction is allowed to occur for a period of time of about 15 minutes to about 30 minutes.
  • the flow of biocompatible material into the reactor chamber may b - 15
  • methyl methacrylate liquid is introduced into a plasma reactor chamber having a plasma-etched or treated body of PMMA where, because of the low pressure within the chamber, the methyl methacrylate vaporizes.
  • the methyl methacrylate is exposed to about 50 to about 150 watts of radio frequency radiation at about 20-30°C where its vapor pressure is about 0.4 to about 0.5 torr.
  • the biocompatible polymeric material is substantially the same as the material forming the substrate.
  • the modified surface should have properties which are relatively nontoxic and nonirritating to living tissues.
  • the modified surface should not adversely affect the desired properties of the remainder of the substrate material, such as structural integrity and optical clarity, among others.
  • the modified surface should be microscopically smooth.
  • the term "microscopically smooth" shall mean that the surface of the modified substrate should be featureless upon examination at an enlargement of about 3,000 to about 10,000x, e.g. by SEM microscopy.
  • the modified surface should show absence of cry ⁇ tallinity, cross-linked and thermally stable. The water contact angle should remain substantially unchanged after grafting of the biocompatible material to the substrate surface.
  • the surface modification of the present invention should not adversely affect the transparency or ocular acuity of the substrate material.
  • the biocompatible material to be grafted to the substrate surface preferably comprises a material that is relatively easy to polymerize in a gas plasma environment. Such materials include unsaturated compounds or those compounds containing nitrogen, silicone or halogen. Materials that are relatively difficult to polymerize in a gas plasma environment include polymers, cyclic compounds, compounds with a high molecular weight, natural polymers such as proteins, and those compounds with extremely high vapor pressures.
  • Novel products having a permanently modified surface resulting from the method of the present invention include prostheses, such as an intraocular lens, for use in mammals having a permanently modified, biocompatible surface, which comprise ⁇ a polymer len ⁇ body and a biocompatible, polymeric material grafted thereto, where the biocompatible, polymeric material comprises substantially the same material as the material forming the polymer lens body, such as PMMA.
  • novel products produced using the method of the present invention include prostheses for use in mammals comprising a polymeric material substrate having a permanently modified surface where the surface was modified by subjecting the substrate surface to radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glas ⁇ transition temperature.
  • Example I An intraocular lens manufactured by Alcon/CILCO from PMMA was abraded using 1 micron aluminum oxide particles to produce grooves on the surface of the lens of 1 micron depth. Macroscopically, the lens had a hazy appearance. The lens was cleaned in a 1% sodium dodecyl sulfate (SDS) solution and then thoroughly rinsed in deionized water to remove any contaminants that may be present from the manufacturing process or subsequent handling. The lens was positioned in a Branson 3000 Series radio frequency plasma reactor in a glass treatment fixture. The pressure inside the reactor was reduced to less than about 0.1 torr for approximately 10 minutes.
  • SDS sodium dodecyl sulfate
  • Argon gas (Ar) was ,then introduced at approximately 8 psi and the pressure inside the reactor was adjusted to 0.5 torr for 10 minutes to purge the chamber with the argon gas. Radio frequency power was then turned on to 120 watts while maintaining chamber pressure at 0.5 torr. Treatment with the argon gas plasma continued for approximately 60 minutes. After this time, radio frequency power was turned off and the chamber was purged to normal atmospheric pressure to open the chamber door. Macroscopically, the lens appeared clean and clear. Upon microscopic examination, some surface irregularities or memory of the initial grooves was apparent.
  • Example II An intraocular lens was treated using the procedures of Example I. After turning off the radio frequency power, the chamber was then pumped down to a pressure of 0.1 torr for approximately 5 minutes to evacuate the chamber. Methylmethacrylate (MMA) monomer was then introduced into the reactor chamber at maximum flow rate (approximately 0.8 torr) and radio frequency power was turned on to 70 watts for 30 minutes. After this time, MMA delivery was discontinued and the radio frequency power was shut down. The chamber was then purged to normal atmospheric pressure to open the chamber door. Macroscopically and microscopically, the lens was free - 18 -
  • MMA Methylmethacrylate
  • Example III A PMMA square sample manufactured by ICI Americas, Inc. of Wilmington, Delaware had a contact angle of 79°. After abrading the sample using aluminum oxide particles having an average diameter of 1 micron to form 1 micron deep grooves on the sample surface, the contact angle was reduced to 77°. The sample was cleaned with a 1% sodium decyl sulphate solution and rinsed with deionized water. The surface of the sample was etched using a Branson 3003-1813 RF plasma reactor by reducing the pressure in the reactor to less than about 0.1 torr for about 10 minutes and then purging the reactor chamber with argon gas at a pressure of 8 psi and reducing the pressure to about 0.5 torr for about 10 minutes.
  • RF power was applied at about 100 watt ⁇ for about 30 minutes while the argon pressure level was maintained at about 0.5 torr.
  • the power supply was discontinued and the chamber evacuated to about 0.1 torr for about 5 minutes.
  • Methylmethacrylate (MMA) monomer was introduced into the reactor to maintain the chamber pressure at about 0.8 torr and the RF power was turned on to 50 watts. After 60 minutes, the MMA delivery and RF power supply were discontinued.
  • the chamber was purged to normal atmospheric pressure.
  • the contact angle of the sample after plasma treatment was 79°, which is equal to the contact angle measured prior to treatment. Therefore, the chemical nature of the surface of the sample was unchanged by grafting the MMA monomer thereto.
  • an untreated Coopervision ® PMMA intraocular lens has a measured contact angle of 74°. 19

Abstract

The surface of a substrate material may be permanently modified so as to develop a microscopically smooth, biocompatible surface thereon. A biocompatible polymeric material may be covalently grafted to the surface of the substrate material by radio frequency plasma-induced grafting. The biocompatible polymeric material is preferably the same as the substrate material but may be different. Before grafting, a portion of the substrate surface may be first removed, as by etching, in a radio frequency plasma reactor using inert argon gas. Alternatively, the surface of the substrate material may be subjected to radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glass transition temperature (Tg) of the substrate material for a time sufficient to produce a microscopically smooth, biocompatible surface on the substrate material. The methods may be used to produce a prosthesis used in mammals, including an intraocular lens, having a polymeric material core and a biocompatible polymeric material covalently grafted to the polymer core by radio frequency plasma treatment.

Description

BIOCOMPATIBLE, SURFACE MODIFIED MATERIALS AND METHOD OF MAKING THE SAME
Field of the Invention The present invention relates to methods of permanently modifying the surface of materials by plasma-induced and, where desired, post-plasma reactions to produce biocompatible, surface modified materials. In addition, the present invention relates to biocompatible, surface modified prostheses and, in particular, to a biocompatible, surface modified intraocular lens used in mammals.
Background of the Invention Prosthetic devices or prostheses are commonly used in medical procedures to replace or augment defective organs in mammals and humans. Such prostheses are numerous and diverse in structure and application. Examples of proεtheses include artificial joints, valve replacements, artificial skin, vascular grafts, shunts, plates and contact and intraocular lenses. Typical prosthetic materials include metals, ceramics, silicone rubbers, polyesters, polyurethanes and/or polysulfones. Synthetic polymers, such as polymethylmethacrylate (PMMA) , silicone elastomers and polymers of hydroxyethylmethacrylate (HEMA) , are preferred polymers for prosthetic use in general and contact lenses and intraocular lenses in particular.
PMMA has several beneficial characteristics for prosthetic use, including excellent light transmission capability, good optical clarity, resistance to fluid diffusion and jln vivo deterioration, ease in processing (injection molding or machining, for example) and ease in implantation.
A problem with typical prior prostheses, such as lens prostheses, is that they are manufactured by machining and also some by injection molding. In the former, the - 2 -
machining process typically leaves circular lathe marks or grooves visible at even relatively low magnification. These machining marks render the lens unusable until the lens surface is smoothed, typically by a mechanical polishing process. However, conventional polishing processes generally take several days to complete, have failure rates in excess of 30% and fail to produce a microscopically smooth surface. The -surfaces of injection molded lenses do not show machine lathe marks. However, their surfaces are also not microscopically smooth and reflect the surface finish of the mold.
Also, typical prosthetic devices comprise natural and/or synthetic materials which are highly irregular on the cellular level. These rough prostheses, especially those which are implanted, can cause tissue irritation, cell proliferation, edema and scarring. For example, posterior lens capsule opacification is a prevalent problem among those patients who have received intraocular lens implants comprising conventionally polished PMMA and other similar materials. Pseudophakic precipitates on the surfaces of an intraocular lens can be indicative of microscopic surface irregularities.
It is desirable to modify the surface properties of such abrasive materials without changing the beneficial characteristics thereof by developing a microscopically smooth surface to discourage tissue adhesion and inhibit unwanted cellular growth. Prostheses which do not promote tissue adhesion, which inhibit cellular growth, and which are not otherwise toxic to living systems may be considered "biocompatible." The biocompatible modified surface should be resistant to deterioration over time and should have no adverse effects on contacting tissues and cells.
Those skilled in the art have long recognized the need for biocompatible, surface modified materials for use in prosthetic devices and other materials. For example, U.S. Patent No. 3,961,379 discloses a bioi plantable device manufactured from a cross-linked, swollen, hydrophilic polymer. These modified polymers must be solid and must be swellable by fluid swelling substances. Once swollen, the solid polymer is polymerized with a modifying substance by, for example, high energy particle radiation. U.S. Patent No. 4,189,364 discloses hydrophilic polymers formed in situ by irradiating a mixture of hydroxyalkyl ethacrylate and a cross-linking agent. This patent discloses a process for forming hydrophilic polymer articles or hydrophilic polymer coatings on other substrates, such as glass or plastic, by polymerizing a hydrophilic monomer system by high energy particulate irradiation, such as accelerated electrons or nuclear particles including neutrons, protons, alpha, beta and/or gamma particles.
Radiation-induced grafting of acrylic acid onto other polymer films is disclosed by Gazard, M. et al.,
"Lithographic Technique Using Radiation-Induced Grafting of Acrylic Acid Into Poly(Methyl Methacrylate) Films, " Polymer Engineering and Science, 20:16 (1980) . Gazard et al. disclose that, under ionizing radiation, polymer properties, such as solubility, may be modified. Ionizing radiation of polymers leads to the formation of free radicals and other intermediates, which may be used to initiate the grafting of a monomer to produce a grafted copolymer with properties different from those of the initial polymer. For example, a grafted copolymer of irradiated PMMA and acrylic acid is insoluble in solvents of PMMA.
U.S. Patent No. 2,999,056 also discloses that an unsaturated organic acid may be attached to a shaped polymeric structure by ionizing radiation. Other methods of altering the surface of polymeric objects include exposing the surface of a polymeric article to low temperature plasma or an electrically charged gaseous atmosphere, followed by contacting the surface of the polymeric article with a surface modifying compound as described, for example, in U.S. Patent No. 4,344,981. This two-step method is generally called plasma-induced coating. Plasma induction has been described generally in U.S. Patent No. 4,328,257, Yaεuda, "Plasma for Modification of Polymers," J. Macromol. Sci. C. Chem.. 10(3) :383 (1978), Mittal, "Interfacial Chemistry and Adhesion: Recent Developments and Prospects," Pure & Appl. Che .. 52:1295 (1980), Akovali, G. and Hasirci, N., "Polymerization of Hexamethyldisiloxane by Plasma on Activated Charcoal: Investigation of Parameters," ^J. Appl. Polymer Sci.. 29:2617 (1984) and Liu, W. T. et al. , "Polymethyl Methacrylate Reεiεt Senεitivity Enhancement in X-Ray Lithography by in Situ Polymerization, " Appl. Phvs. Lett.. 44:973 (1984), for example.
Ionized vapor or a plasma discharge is typically created in a vacuum chamber in which the object to be modified is placed. The plasma discharge conditions the surface of the object by creating free radicals and/or ions. It is known, for example, that exposing the surface of an object to a plasma discharge, such as an oxygen plasma, enhances the wettability or hydrophilicity of such a surface. However, such treatment is only temporary. U.S. Patent Nos. 3,925,178; 3,944,709; 4,072,769; 4,096,315; 4,122,942; 4,123,308; 4,131,691; 4,137,365; 4,214,014 and 4,478,873 disclose examples of polymers whose surface characteristics have been modified by a plasma discharge.
Plasma discharge treatment may also be used to prepare an object for the attachment or grafting of a compound or material to the plasma discharge treated object. For example, a plasma discharge step may be used to condition the surface for grafting by creating free radicals to which a compound or material may be grafted. Such compounds or materials are generally called surface modifiers. Knight, P. M. et al., in "Surface Modification of Intraocular Lenses to Reduce Corneal Endothelial Damage," Am. Intra-ocular Implants Soc. J. , 5:123 (1979) disclose one example of a polymer object having a surface modifier attached thereto using gamma irradiation and radio frequency (RF) gas plasma treatment to generate free radicals on the surface of a PMMA intraocular - 5 -
lens followed by polymerizing hydrophilic monomers, in particular, HEMA and vinyl pyrrolidone, as a coating on the surface of the lens. While the coated surfaces exhibited enhanced hydrophilicity, the coated surfaces were not stable when sterilized by boiling. Surface modification by gamma radiation followed by polymerization on the surface, on the other hand, remained intact through several hours of boiling. However, such coated PMMA surfaces were damaging to rabbit endothelial cells and surfaces coated with dissolvable coatings, such as polyvinyl acetate, were preferred.
Another example of a surface treated polymer is disclosed in U.S. Patent No. 4,312,575. This patent discloses a soft, highly oxygen permeable, hydrophobic polymeric lens which has a surface coating of an ultra-thin, optically clear, permeable barrier. The coating is the reaction product reεulting from a glow discharge polymerization process conducted in a hydrocarbon or halogenated hydrocarbon gaseous atmosphere. While the plasma discharge process, itself, results in a hydrophilic surface, this patent discloses that subsequent exposure to a glow discharge atmosphere of oxygen or ambient oxygen yields a still more hydrophilic surface.
U.S. Patent 4,409,258 discloses a method for rendering contact lenses hydrophilic by bombarding the lens of PMMA or silicone, for example, with a positive ion beam generated by a plasma discharge, such as an oxygen plasma. The lens is thereafter hydrated, preferably at an elevated temperature.
Examples of surface treated polymeric lenses for use in humans are included in U.S. Patent No. 3,880,818. This patent discloses a soft contact lens that is flexible and physiologically compatible. The lens is made by manufacturing a hard, inflexible prepolymer, such as a hard acrylic acid-type polymer, and reacting the inflexible prepolymer wit an alcohol to esterify pendant carboxyl groups with alkyl groups, hydroxy alkyl groups or alkoxyalkyl groups, containin no more than eleven carbon atoms. - 6 -
U.S. Patent No. 4,143,949 discloses a discharge polymerization and coating process for making a hydrophilic contact lens from an oxygen permeable, hydrophobic polymer. The hydrophobic lens is placed in a glow discharge apparatus containing an atmosphere comprising a polymerizable organic monomer, such as hydroxyalkyl acrylate or methacrylate, glycidyl methacrylate, propylene oxide or N-vinyl-2-pyrrolidone. The glow discharge is used to polymerize the monomer onto the surface of the contact lens. Other examples of surface treated polymeric objects include U.S. Patent Nos. 3,228,741; 3,959,105; 3,985,697; 4,055,378; 4,277,595; 4,405,773; 4,430,458; 4,463,148; and 4,731,080. U.S. Patent No. 4,731,080, for example, discloses a coated intraocular lens having a hydrophobic crosε-linked vinyl-containing silicone polymer placed on the lens surface in solution.
It would be desirable to have a biocompatible, surface modified material and a method for producing the same, wherein the surface of the substrate material is cleaned, and active species, such as ions and free radicals, are produced on the surface by a plasma treatment to enhance subsequent grafting of a polymeric biocompatible material to the substrate surface to provide a substantially permanent, smoot surface on a cellular level. A method for grafting a polymeric biocompatible material to the surface of a substrat is disclosed in our U.S. Patent No. 5,080,924. By pretreatin the surface of the substrate material, the smoothness of the substrate and the grafted surface may be improved.
Brief Summary of the Invention According to the present invention, a method is provided for permanently modifying a surface of a polymeric substrate material so that the substrate material develops a microscopically smooth, biocompatible surface. The method comprises covalently grafting a biocompatible polymeric material to the surface of the substrate material by radio 7 -
frequency plasma treatment. The biocompatible polymeric material comprises substantially the same material as the polymeric substrate. In one embodiment, before the grafting, at least a portion of the surface of the polymeric substrate material is removed, such as by etching.
Another aspect of the present invention is another method for permanently modifying a surface of a substrate polymeric material. The method comprises subjecting at least a portion of the surface of the polymeric substrate material to inert gas radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glass transition temperature (Tg) of the substrate material for a time sufficient to produce surface relaxation and a resulting microscopically smooth, biocompatible surface on the substrate material.
Yet another aspect of the present invention is a prostheses used in mammals which has a permanently modified microscopically smooth, biocompatible surface. The prostheses comprises a polymeric material core and a biocompatible material grafted to the surface of a polymer core by radio frequency plasma treatment. The biocompatible polymeric material comprises substantially the same material as the core.
Another aspect of the present invention is an intraocular lens having a permanently modified, smooth, biocompatible surface. The lens comprises a polymeric material lens body having a biocompatible polymeric material. The biocompatible polymeric material is grafted to the surface of the lens body and comprises substantially the same material as the body.
A further aspect of the present invention is a method of manufacturing a prostheses to provide the prostheses with a microscopically smootlj, biocompatible surface without the use of mechanical polishing. The method comprises covalently -grafting a polymeric biocompatible material to the - 8
surface of the core by radio frequency plasma treatment. The surface to be grafted may first be etched.
Brief Description of the Drawing The foregoing summary, as well as the following detailed description of the preferred embodiments, will be better understood when read in conjunction with the appended "drawing. For the purpose of illustrating the invention, there is shown in the drawing one embodiment, it being understood, however, that the invention is not limited to the specific method and instrumentality disclosed. In the drawing:
Fig. 1 is a graph of surface temperature of PMMA substrates as a function of time at various radio frequency power levels which shows the thermal annealing effect of argon plasma where the temperature of the substrate surface increases with plasma power and can be made to exceed the glass transition temperature, according to one embodiment of the present invention.
Detailed Description of Preferred Embodiments Although the methods of modifying the surface of a polymeric substrate material according to the present invention apply generally to many different materials, the methods are described and examples are given below for polymeric intraocular lenses as prostheses which may be used in mammals. It will be understood by one of ordinary skill in the art that the methods of the present invention may be used to prepare permanently modified surfaces of other substrate materials, such as those prostheεtic materials identified above. Moreover, it will be apparent to an ordinary skilled artisan that the methods of the present invention readily lend themselves to the preparation of materials having modified or enhanced surface characteristics having other uses.
Examples of polymeric substrate materials which are useful in the present invention include polymers, such as silicone elastomers, polypropylene, polyesters, such as polyethylene terephthalate, polytetrafluoroethylene, polyurethane, PMMA, polyacrylic acid, and polymers of diethylenetriamine, allylamine, HEMA, ethylenedia ine, hexamethyl-disiloxane, silazane and N-vinyl pyrrolidone. Generally, the substrate material used in accordance with the present invention is chosen dependent upon its intended use. For example, PMMA, HEMA and silicone are useful for making prosthetic devices intended for implantation or other applications in mammals. However, in view of the present specification, one of ordinary skill in the art will appreciate that any biocompatible organic polymer may be used as a substrate material, as well as certain ceramics. Where an optically clear polymer for use in prosthetic devices for mammals is deεired as the substrate material, it is presently preferred that the polymer comprise PMMA or a silicone elastomer.
According to one embodiment of the method of the present invention, at least a portion of the surface of the polymeric substrate material is removed to clean the substrate and produce active species on the polymer surface, such as ions and free radicals, which can be used for inducing a grafted reaction. Preferably, the removal of the portion of the surface material is accomplished by inert gas etching. The etching may be induced in a radio frequency (RF) plasma reactor, such as are well known to those of ordinary skill in the art. The Branson Model 3003-1813 is one example of a suitable radio frequency gas plasma reactor which may be used to etch the surface of the polymeric substrate material. One skilled in the art will appreciate, however, that other plasma reactors and apparatus may be used in accordance with the present invention.
Generally, the rate of material removal is influenced by the frequency or power of the gas plasma, the treatment time, the gas used in the plasma reactor, the gas pressure/concentration and the type of bond present on the treated substrate material surface, depending on the particular substrate material. For the Branson Model 3003-1813 radio frequency plasma reactor, frequency is kept at 13.56 MHz, which is suitable for etching.
Preferably, the etching process includes injecting a noble or ambient gas into the reactor to create ions which bombard the substrate creating active sites on the substrate .surface. Nitrogen and ammonia gases are also believed to be useful in the radio frequency gas plasma reaction when nitrogenous compounds are desired. Preferably, the noble gas is argon, which createε active sites on the substrate surface but does not produce new chemical groups when applied to the substrate surface in a RF gas.plasma reactor. Where no biocompatible material is to be grafted to the substrate surface (discussed below) or where the presence of new chemical groups on the substrate surface is not desired, it is presently preferred to use a noble gas, such as argon, as the RF gas in the plasma reactor. Oxygen, on the other hand, for example, tends to produce peroxides in such plasma-induced grafting reactions and is, therefore, generally less stable chemically. One of ordinary skill in the art will be readily able to determine in view of this disclosure suitable gases which may be used in the plasma reaction in accordance with the present invention.
The substrate surface to be etched is first cleaned with a mild soap solution, i.e., a 1% sodium decyl sulphate solution, and rinsed in deionized water to remove any contaminants that may be present from the manufacturing processes and subsequent handling. The lens or other substrate is positioned in the radio frequency plasma reactor on a glasε or other suitable fixture. The pressure in the reactor is reduced to less than about 0.05 to about 0.1 torr for about 5 to about 10 minutes. Argon gas is introduced into the chamber at a pressure of about 8 to about 10 psi and the pressure within the reaction chamber is adjusted to about 0.3 to about 0.5 torr for about 5 to about 10 minuteε to purge the chamber with the argon gas. Radio frequency power was - 11
applied at about 50 to about 200 watts for about 30 to about 60 minutes while maintaining the pressure level at about 0.3 to about 0.5 torr. The RF power supply is discontinued and the chamber is maintained at a pressure of about 0.3 to about 0.5 torr for about 5 to about 10 minutes. One of ordinary skill in the art would understand that the pressure levels, power levels and times may vary based upon such variableε as the substrate material, different reactors, and the choice of ambient gas. In one embodiment of the present method, after etching of the substrate surface, the substrate surface may be subjected to radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glass transition temperature (Tg) of the substrate material for a time sufficient to produce a microscopically smooth, biocompatible surface on the substrate material.
While not wishing to be bound by any particular theory, the inventors believe that plasma treatment to induce an increase in temperature causes a thermal annealing at the surface of the substrate whereby irregular surface features (such as surface peaks, etc.) relax, evening out such irregularities.
Fig. 1 is a graph of substrate surface temperature of PMMA substrates as a function of time at several power levels ranging from 30 to 150 watts. As shown in Fig. 1, the temperature of the substrate surface increases during plasma treatment. For example, at 150 watts of power, the temperature of the substrate climbs about 60°C after 10 minutes of plasma treatment. Where temperatures above the glass transition temperature are desired, relatively higher radiation power is preferred. For example, to reach a surface temperature of about 105°C, which is the glass transition temperature of PMMA, radiation power of about 120 to about 150 watts is preferred. ^One skilled in the art may readily determine glass transition temperature (Tg) by reference to publicly available - 12
material characteristic tables and experimentally determine the temperature obtainable at a given wattage in a given reactor. Other temperatures can then be calculated by factoring in time, efficiency of the reaction chamber, the surface area of the substrate and reactor power, for example. The radiation power used and the time the substrate is exposed to such radiation should be such to avoid subsurface thermal -circulation and melting of the substrate.
In an alternative embodiment, with or without prior surface removal (etching) , the method includes a step of covalently grafting a polymeric biocompatible material to the surface of the substrate material by radio frequency plasma treatment. Preferably, the biocompatible polymeric material is introduced in the monomer form and is selected from ethylenediamine, hexamethyldisiloxane, acrylic acid, diethylenetriamine, allylamine, hydroxyethylmethacrylate, methylmethacrylate and combinations thereof, for example. Polymeric grafts of silicone, polypropylene, polyester, polytetrafluoroethylene, polyethylene terephthalate or polyurethane may be similarly formed on the surface of the substrate material by appropriate reaction.
The resulting biocompatible polymeric material is preferably grafted to the βubstrate material in a relatively uniform thickness and texture along the surface of the substrate material. In addition, especially where it is desired to use the substrate material as a prosthetic lens, it is preferred that the biocompatible polymeric material is present on the surface of the substrate material in a relatively uniform, small thickness to prevent 'interference with the optical clarity of the lens. More preferably, the biocompatible polymeric material is present in few molecular layers. In one embodiment of the present invention, for example, a surface modified substrate comprises a biocompatible polymeric material grafted to the surface of a substrate material with a biocompatible polymeric material thickness of about lOOΛ. Grafting of the biocompatible polymeric material according to the present invention is conducted using radio frequency plaεma-induced grafting. Other methods of grafting, such as electron beam or ultra-violet (UV) radiation, are not suitable where it is desired to modify only the surface of th substrate material. For example, where a prosthetic lens, such as a contact lens or intraocular lens, is desired to be modified, modification should be confined to the surface of the lens to avoid affecting the optical properties of the lens. Radio frequency plasma-induced grafting according to the present invention avoids structural modification below th outer-most surface layer, and generally results in more desirable optical properties'.
Such gas plasma-induced grafting may be conducted i a radio frequency gas plasma reactor such as that discussed above capable of generating a frequency of about 1 MHz to about 40 MHz. The frequency generated by a typical commercia gas plasma reactor is 13.56 MHz, although one skilled in the art will recognize that higher and lower frequencies may be used to graft the biocompatible polymeric material to the surface of the substrate material in a radio frequency gas plasma reactor, depending on the substrate material and biocompatible polymeric material used, the relative ease or difficulty in preparing the surface of the substrate material for grafting, the relative ease or difficulty of vaporizing o polymerizing the biocompatible material, among other factors. The length of time the biocompatible material in an induced plasma state should be allowed to react with the substrate material depends upon several factors, including th plasma or radiation power, the radio frequency, the flow concentration or pressure, the temperature and the desired thickness of the grafted material. Preferably, the radiation power is about 10 watts to about 200 watts, depending upon th biocompatible material. For example, where the biocompatible material comprises silazane, hexamethyldisiloxane, MMA, NVP o AA, it is presently preferred that the radiation power is - 14 -
about 50 watts. Where the biocompatible layer material comprises HEMA (discussed below) , it is presently preferred that the radiation power is about 10 watts to about 200 watts. In any event, except where desired, the reactor power used and the duration during which such power is used should be low and/or short enough so as to not induce thermal circulation and melt the substrate surface. For example, where the substrate material comprises PMMA, the reaction conditions (i.e., power and duration) should not increase the temperature of the subεtrate material above about 40°-60°C. One skilled in the art may readily determine, in view of the plasma reaction variables described above, the desired plasma radiation power to be used in accordance with the present invention. The temperature in the plasma reaction should not b allowed to approach those temperatures which may structurally damage the substrate material or the biocompatible material. High radiation power and any polymerization reaction (i.e., polymerization which may occur when the grafting reaction occurs; e.g.: polymerization to polymethylmethacrylate) tend to increase the temperature of the plasma reaction zone. It is desirable, therefore, to maintain the temperature in the plasma reaction below the temperature at which the substrate material and/or the graft material will be damaged, typically below about 60°-80°C.
The flow concentration or vapor pressure of the plasma reactants in the reactor chamber should be low enough so that the particular monomer of the biocompatible material vaporizes when introduced into the reactor. Preferably, the vapor pressure is about 0.1 torr to about 0.6 torr. More preferably, the vapor pressure is about 0.4 torr.
The plasma reaction is preferably conducted for a period of time of about 1 minute to about 60 minutes.' More preferably, the plasma reaction is allowed to occur for a period of time of about 15 minutes to about 30 minutes. The flow of biocompatible material into the reactor chamber may b - 15
continued for a period of time after the RF power supply to the reactor is terminated. The continued supply of biocompatible material is believed to quench long-lived radicals that could be present on some substrates. In view of this disclosure, one skilled in the art may readily determine the reactants, time, pressure and temperature conditions for a reaction using given materials without undue experimentation. For example, in one embodiment of the present invention, methyl methacrylate liquid is introduced into a plasma reactor chamber having a plasma-etched or treated body of PMMA where, because of the low pressure within the chamber, the methyl methacrylate vaporizes. The methyl methacrylate is exposed to about 50 to about 150 watts of radio frequency radiation at about 20-30°C where its vapor pressure is about 0.4 to about 0.5 torr.
Where it is desired to have no change in the substrate surface chemistry, the biocompatible polymeric material is substantially the same as the material forming the substrate. Once the substrate material surface has been modified by covalently grafting the biocompatible material to the surface of the substrate material, the modified surface should have properties which are relatively nontoxic and nonirritating to living tissues. In addition, the modified surface should not adversely affect the desired properties of the remainder of the substrate material, such as structural integrity and optical clarity, among others. In addition, the modified surface should be microscopically smooth. As used herein, the term "microscopically smooth" shall mean that the surface of the modified substrate should be featureless upon examination at an enlargement of about 3,000 to about 10,000x, e.g. by SEM microscopy. In addition, where desired, and depending on the properties of the biocompatible polymeric material, the modified surface should show absence of cryεtallinity, cross-linked and thermally stable. The water contact angle should remain substantially unchanged after grafting of the biocompatible material to the substrate surface.
Where the substrate material is intended for use in or as a prosthetic device, such as an intraocular lens, the surface modification of the present invention should not adversely affect the transparency or ocular acuity of the substrate material. Further, the biocompatible material to be grafted to the substrate surface preferably comprises a material that is relatively easy to polymerize in a gas plasma environment. Such materials include unsaturated compounds or those compounds containing nitrogen, silicone or halogen. Materials that are relatively difficult to polymerize in a gas plasma environment include polymers, cyclic compounds, compounds with a high molecular weight, natural polymers such as proteins, and those compounds with extremely high vapor pressures.
Novel products having a permanently modified surface resulting from the method of the present invention include prostheses, such as an intraocular lens, for use in mammals having a permanently modified, biocompatible surface, which compriseε a polymer lenε body and a biocompatible, polymeric material grafted thereto, where the biocompatible, polymeric material comprises substantially the same material as the material forming the polymer lens body, such as PMMA. In addition, novel products produced using the method of the present invention include prostheses for use in mammals comprising a polymeric material substrate having a permanently modified surface where the surface was modified by subjecting the substrate surface to radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glasε transition temperature.
The invention will now be illustrated in further detail by reference to the following specific, non-limiting examples. Example I An intraocular lens manufactured by Alcon/CILCO from PMMA was abraded using 1 micron aluminum oxide particles to produce grooves on the surface of the lens of 1 micron depth. Macroscopically, the lens had a hazy appearance. The lens was cleaned in a 1% sodium dodecyl sulfate (SDS) solution and then thoroughly rinsed in deionized water to remove any contaminants that may be present from the manufacturing process or subsequent handling. The lens was positioned in a Branson 3000 Series radio frequency plasma reactor in a glass treatment fixture. The pressure inside the reactor was reduced to less than about 0.1 torr for approximately 10 minutes. Argon gas (Ar) was ,then introduced at approximately 8 psi and the pressure inside the reactor was adjusted to 0.5 torr for 10 minutes to purge the chamber with the argon gas. Radio frequency power was then turned on to 120 watts while maintaining chamber pressure at 0.5 torr. Treatment with the argon gas plasma continued for approximately 60 minutes. After this time, radio frequency power was turned off and the chamber was purged to normal atmospheric pressure to open the chamber door. Macroscopically, the lens appeared clean and clear. Upon microscopic examination, some surface irregularities or memory of the initial grooves was apparent.
Example II An intraocular lens was treated using the procedures of Example I. After turning off the radio frequency power, the chamber was then pumped down to a pressure of 0.1 torr for approximately 5 minutes to evacuate the chamber. Methylmethacrylate (MMA) monomer was then introduced into the reactor chamber at maximum flow rate (approximately 0.8 torr) and radio frequency power was turned on to 70 watts for 30 minutes. After this time, MMA delivery was discontinued and the radio frequency power was shut down. The chamber was then purged to normal atmospheric pressure to open the chamber door. Macroscopically and microscopically, the lens was free - 18 -
of any surface irregularities, surpassing the surface quality of the original, commercial lens.
Example III A PMMA square sample manufactured by ICI Americas, Inc. of Wilmington, Delaware had a contact angle of 79°. After abrading the sample using aluminum oxide particles having an average diameter of 1 micron to form 1 micron deep grooves on the sample surface, the contact angle was reduced to 77°. The sample was cleaned with a 1% sodium decyl sulphate solution and rinsed with deionized water. The surface of the sample was etched using a Branson 3003-1813 RF plasma reactor by reducing the pressure in the reactor to less than about 0.1 torr for about 10 minutes and then purging the reactor chamber with argon gas at a pressure of 8 psi and reducing the pressure to about 0.5 torr for about 10 minutes. RF power was applied at about 100 wattε for about 30 minutes while the argon pressure level was maintained at about 0.5 torr. The power supply was discontinued and the chamber evacuated to about 0.1 torr for about 5 minutes. Methylmethacrylate (MMA) monomer was introduced into the reactor to maintain the chamber pressure at about 0.8 torr and the RF power was turned on to 50 watts. After 60 minutes, the MMA delivery and RF power supply were discontinued. The chamber was purged to normal atmospheric pressure. The contact angle of the sample after plasma treatment was 79°, which is equal to the contact angle measured prior to treatment. Therefore, the chemical nature of the surface of the sample was unchanged by grafting the MMA monomer thereto. For purposeε of comparison, an untreated Coopervision® PMMA intraocular lens has a measured contact angle of 74°. 19
TABLE I Treatment
ICI-PMMA sample without plasma treatment after abrasion after plasma treatment
Figure imgf000021_0001
Coopervision-PMMA lens without plasma treatment 74°
The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof and, accordingly, reference should be made to the appended claims, rather than the specification, as indicating the scope of the invention.

Claims

- 20 -CLAIMS
1. A method of permanently modifying a εurface of a polymeric substrate material to produce a microscopically smooth, biocompatible surface thereon, comprising covalently grafting a polymeric biocompatible material to the surface of the polymeric substrate material by radio frequency plasma treatment, the biocompatible polymeric material comprising substantially the same material as the polymeric substrate.
2. The method according to claim 1, wherein the polymeric substrate material is selected from the group consisting of polyacrylic acid, silicone elastomer, polypropylene, polyester, polyethylene terephthalate, polytetrafluoroethylene, polyurethane and polymethyl- methacrylate, and polymers of ethylenedia ine, diethylenetriamine, HEMA, allylamine, hexamethydisiloxane, silazane and N-vinyl pyrrolidone.
3. The method according to claim 1 further comprising the step of removing at least a portion of the surface of the polymeric substrate material prior to said covalent grafting.
4. The method according to claim 3, wherein the portion of the surface of the polymeric substrate material is removed by etching.
5. The method according to claim 4, wherein the etching is induced in a radio frequency plasma reactor.
6. The method according to claim 5, wherein the etching includes injecting a noble gas into the reactor.
7. The method according to claim 6, wherein the noble gas is argon.
8. The method according to claim 1, wherein the grafting is induced in a radio frequency plasma reactor generating a frequency of about 1 MHz to about 40 MHz.
9. The method according to claim l, wherein the biocompatible polymeric material grafted to the substrate is selected from the group consisting of monomers of ethylenediamine, hexamethyldisiloxane, acrylic acid, - 21 -
diethylenetriamine, allylamine, hydroxyethylmethacrylate and methylmethacrylate to form polymeric grafts.
10. A method of permanently modifying a surface of a polymeric substrate material, comprising subjecting the substrate surface to radio frequency plasma sufficient to raise the temperature at the substrate surface to just above the glass transition temperature of the substrate material surface for a time sufficient to produce a microscopically smooth, biocompatible surface on the substrate material.
11. The method according to claim 10, wherein the polymeric substrate material is selected from the group consisting of polyacrylic acid, silicone elastomer, polypropylene, polyester, polyethylene terephthalate, polytetrafluoroethylene, polyurethane, polymethylmethacrylate, and polymers of ethylenediamine, diethylenetriamine, HEMA, allyhamine, hexamethyldisiloxane, silazane, and N-vinyl pynolidone.
12. The method according to claim 10 further comprising the step of removing at least a portion of the surface of the polymeric substrate material.
13. The method according to claim 12, wherein the portion of the surface of the polymeric substrate material is removed by etching.
14. The method according to claim 13, wherein the etching includes injecting a noble gas into the reactor.
15. The method according to claim 14, wherein the noble gas is argon.
16. The method according to claim 15, wherein the radio frequency plasma reactor operates at a power of about 100 watts to about 200 watts.
17. The method according to claim 12, further comprising covalently grafting a polymeric biocompatible material to the surface of the polymeric substrate material b radio frequency plasma treatment. 22 -
18. The method according to claim 17, wherein the grafting is induced in a radio frequency plasma reactor generating a frequency of about 1 MHz to about 40 MHz.
19. A prosthesis for use in mammals comprising a polymeric material as permanently modified using the method according to claim 10.
20. A prostheεiε used in mammals having a permanently modified, microscopically smooth, biocompatible surface comprising:
(a) a polymeric material core; and
(b) a biocompatible polymeric material grafted to the surface of the polymer core by radio frequency plasma treatment, the biocompatible polymeric material comprising substantially the same material as the core.
21. The prostheεiε according to claim 20, wherein the biocompatible polymeric material grafted to the core is selected from the group consiεting of monomerε of ethylenediamine, acrylic acid, diethylene triamine, allylamine, hexamethyldisiloxane, hydroxyethylmethacrylate, and methylmethacrylate to form polymeric grafts.
22. An intraocular lens having a permanently modified, smooth, biocompatible surface, comprising a polymeric material lens body having an etched surface, and a biocompatible polymeric material, said biocompatible polymeric material being grafted to the surface of the lens body and comprising substantially the same material as the body.
23. A method of manufacturing a prosthesis comprising providing a polymeric prosthesiε core and covalently grafting a polymeric biocompatible material to a surface of the core by radio frequency plasma treatment, whereby the prosthesis is provided with a microscopically smooth, biocompatible surface.
24. The method according to claim 23 further comprising the step of etching the surface of the polymeric prosthesiε core prior to covalently grafting the polymeric biocompatible material thereto.
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005023018A1 (en) * 2005-05-19 2006-11-23 Rehau Ag + Co. Modification of silicone rubber objects to produce a non-stick surface, e.g. on tubing for catheters or other medical uses, involves depositing a silicate-containing functional layer on the surface from a flame
WO2006122744A1 (en) 2005-05-19 2006-11-23 Rehau Ag + Co Method for modifying a silicone rubber surface
DE102005023017A1 (en) * 2005-05-19 2006-11-23 Rehau Ag + Co Silicone rubber objects with a non-stick surface, e.g. tubing for catheters or other medical uses, obtained by modifying the surface with a silicate-containing functional layer formed by deposition from a flame
EP2335917A1 (en) * 2008-09-26 2011-06-22 National University Corporation Tokyo Medical and Dental University Polymer brush composite and method for producing same
US8974054B2 (en) 2012-02-01 2015-03-10 Lenswista Ag Contact lens

Families Citing this family (108)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6514238B1 (en) * 1989-08-14 2003-02-04 Photogenesis, Inc. Method for preparation and transplantation of volute grafts and surgical instrument therefor
SG49267A1 (en) 1989-08-14 1998-05-18 Photogenesis Inc Surgical instrument and cell isolation and transplantation
US5817075A (en) * 1989-08-14 1998-10-06 Photogenesis, Inc. Method for preparation and transplantation of planar implants and surgical instrument therefor
US6045791A (en) * 1992-03-06 2000-04-04 Photogenesis, Inc. Retinal pigment epithelium transplantation
AU6639194A (en) * 1993-04-23 1994-11-21 Etex Corporation Method of coating medical devices and devices coated thereby
US5618316A (en) * 1993-12-14 1997-04-08 Hoffman; Allan S. Polyethylene oxide coated intraocular lens
DK0693975T4 (en) * 1994-02-16 2003-08-18 Coca Cola Co Hollow containers with inert or impermeable inner surface through plasma supported surface reaction or surface polymerization
US6149982A (en) * 1994-02-16 2000-11-21 The Coca-Cola Company Method of forming a coating on an inner surface
US5487920A (en) * 1994-04-19 1996-01-30 The Boc Group, Inc. Process for plasma-enhanced chemical vapor deposition of anti-fog and anti-scratch coatings onto various substrates
WO1996008211A2 (en) * 1994-09-09 1996-03-21 Surface Engineering Technologies, Division Of Innerdyne, Inc. Plasma grafting methods and compounds
US5507804A (en) * 1994-11-16 1996-04-16 Alcon Laboratories, Inc. Cross-linked polyethylene oxide coatings to improve the biocompatibility of implantable medical devices
MX9705922A (en) * 1995-02-01 1997-10-31 Schneider Usa Inc Process for hydrophilicization of hydrophobic polymers.
US5868728A (en) * 1995-02-28 1999-02-09 Photogenesis, Inc. Medical linear actuator for surgical delivery, manipulation, and extraction
US6514573B2 (en) * 1996-02-21 2003-02-04 Commonwealth Scientific And Industrial Research Organisation Method for reducing crazing in a plastics material
US5985524A (en) * 1997-03-28 1999-11-16 International Business Machines Incorporated Process for using bilayer photoresist
GB9717368D0 (en) * 1997-08-18 1997-10-22 Crowther Jonathan Cold plasma metallization
WO1999057179A1 (en) 1998-05-05 1999-11-11 Bausch & Lomb Incorporated Surface treatment of silicone hydrogel contact lenses
GB9902823D0 (en) 1998-12-23 1999-03-31 Dow Corning Sa Biocompatible coatings
US6213604B1 (en) 1999-05-20 2001-04-10 Bausch & Lomb Incorporated Plasma surface treatment of silicone hydrogel contact lenses with a flexible carbon coating
ATE286685T1 (en) * 1999-09-02 2005-01-15 Alcon Inc HYDROPHILIC COATING AGENT, HYDROPHOBIC BONDED TO SURGICAL IMPLANTS
ES2315953T3 (en) * 1999-09-02 2009-04-01 Alcon, Inc. HYDROPHILE COATING COMPOSITIONS WITH COVALENT LINK FOR IMPLANTS.
DE19953667B4 (en) * 1999-11-08 2009-06-04 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Layer with selectively functionalized surface, process for the preparation and their use
US6543984B1 (en) 2000-03-31 2003-04-08 Bausch & Lomb Incorporated Lens transfer method and devices
DE10017846C2 (en) * 2000-04-11 2002-03-14 Fraunhofer Ges Forschung Method of depositing and using a polymer layer
GB2399020B (en) * 2002-02-14 2005-01-12 Photogenesis Inc Subretinal implantation device and surgical cannulas for use therewith
GB0206932D0 (en) * 2002-03-23 2002-05-08 Univ Durham Preparation of superabsorbent materials by plasma modification
EP1462183A1 (en) * 2003-03-28 2004-09-29 Sulzer Markets and Technology AG Method of treating the surface of a substrate and substrate thus treated
US7138187B2 (en) * 2004-03-19 2006-11-21 Younger Mfg. Co. Polyvinyl alcohol-based film exhibiting improved adhesion
US7501039B2 (en) * 2004-06-17 2009-03-10 The Ohio State University Gas assisted bonding of polymers and polymer composites
US20080038710A1 (en) * 2004-06-17 2008-02-14 The Ohio State University Assemblies incorporating biomolecules and/or cells with micro-/nanostructures, and methods of making the same for biological applications
US20060287486A1 (en) 2005-06-17 2006-12-21 Crawford Emmett D Optical media comprising polyester compositions formed from 2,2,4,4-tetramethyl-1,3-cyclobutanediol and 1,4-cyclohexanedimethanol
US20100184940A1 (en) * 2005-03-02 2010-07-22 Eastman Chemical Company Polyester Compositions Which Comprise Cyclobutanediol and Certain Thermal Stabilizers, and/or Reaction Products Thereof
US7704605B2 (en) * 2006-03-28 2010-04-27 Eastman Chemical Company Thermoplastic articles comprising cyclobutanediol having a decorative material embedded therein
EP1937225B1 (en) * 2005-08-12 2016-12-07 The Procter and Gamble Company Coated substrate with properties of keratinous tissue
US20070106054A1 (en) * 2005-10-28 2007-05-10 Crawford Emmett D Polyester compositions containing cyclobutanediol having a certain combination of inherent viscosity and high glass transition temperature and articles made therefrom
US8586701B2 (en) * 2005-10-28 2013-11-19 Eastman Chemical Company Process for the preparation of copolyesters based on 2,2,4,4-tetramethyl-1,3-cyclobutanediol and 1,4-cyclohexanedimethanol
US8193302B2 (en) 2005-10-28 2012-06-05 Eastman Chemical Company Polyester compositions which comprise cyclobutanediol and certain phosphate thermal stabilizers, and/or reaction products thereof
EP1940909B1 (en) * 2005-10-28 2009-10-07 Eastman Chemical Company Restaurant smallware comprising polyester compositions formed from 2,2,4,4-tetramethyl-1,3-cyclobutanediol and 1,4-cyclohexanedimethanol
PL1940955T3 (en) * 2005-10-28 2011-04-29 Eastman Chem Co Polyester compositions which comprise cyclobutanediol and certain thermal stabilizers, and/or reaction products thereof
US9598533B2 (en) 2005-11-22 2017-03-21 Eastman Chemical Company Polyester compositions containing cyclobutanediol having a certain combination of inherent viscosity and moderate glass transition temperature and articles made therefrom
US7737246B2 (en) 2005-12-15 2010-06-15 Eastman Chemical Company Polyester compositions which comprise cyclobutanediol, cyclohexanedimethanol, and ethylene glycol and manufacturing processes therefor
WO2007095549A2 (en) * 2006-02-13 2007-08-23 Medtronic, Inc. Medical devices having textured surfaces
US9169388B2 (en) 2006-03-28 2015-10-27 Eastman Chemical Company Polyester compositions which comprise cyclobutanediol and certain thermal stabilizers, and/or reaction products thereof
US20080143955A1 (en) * 2006-12-15 2008-06-19 Bausch & Lomb Incorporated Silicone Contact Lenses with Silicate Coating
US7625598B2 (en) * 2006-12-15 2009-12-01 Bausch & Lomb Incorporated Silicone contact lenses with wrinkled surface
US20080206481A1 (en) * 2007-02-26 2008-08-28 Bausch & Lomb Incorporated Silicone contact lenses with wrinkled surface
US8501287B2 (en) 2007-11-21 2013-08-06 Eastman Chemical Company Plastic baby bottles, other blow molded articles, and processes for their manufacture
KR101895184B1 (en) 2007-11-21 2018-09-04 이스트만 케미칼 컴파니 Plastic baby bottles, other blow molded articles, and processes for their manufacture
US8198371B2 (en) 2008-06-27 2012-06-12 Eastman Chemical Company Blends of polyesters and ABS copolymers
US20100099828A1 (en) * 2008-10-21 2010-04-22 Eastman Chemical Company Clear Binary Blends of Aliphatic Polyesters and Aliphatic-Aromatic Polyesters
US8895654B2 (en) * 2008-12-18 2014-11-25 Eastman Chemical Company Polyester compositions which comprise spiro-glycol, cyclohexanedimethanol, and terephthalic acid
US20110082543A1 (en) * 2009-10-06 2011-04-07 Cleo Cosmetic And Pharmaceutical Company, Llc Methods and Devices for Preventing or Delaying Posterior Capsule Opacification
US8420869B2 (en) 2010-12-09 2013-04-16 Eastman Chemical Company Process for the preparation of 2,2,4,4-tetraalkylcyclobutane-1,3-diols
US8420868B2 (en) 2010-12-09 2013-04-16 Eastman Chemical Company Process for the preparation of 2,2,4,4-tetraalkylcyclobutane-1,3-diols
US8394997B2 (en) 2010-12-09 2013-03-12 Eastman Chemical Company Process for the isomerization of 2,2,4,4-tetraalkylcyclobutane-1,3-diols
ES2474572T3 (en) * 2012-02-01 2014-07-09 Lenswista Ag Silicone contact lens
US20130217830A1 (en) 2012-02-16 2013-08-22 Eastman Chemical Company Clear Semi-Crystalline Articles with Improved Heat Resistance
US8545951B2 (en) 2012-02-29 2013-10-01 Kimberly-Clark Worldwide, Inc. Endotracheal tubes and other polymer substrates including an anti-fouling treatment
US8798332B2 (en) 2012-05-15 2014-08-05 Google Inc. Contact lenses
US20140012115A1 (en) * 2012-07-03 2014-01-09 Medtronic Minimed, Inc. Plasma deposited adhesion promoter layers for use with analyte sensors
US9158133B1 (en) 2012-07-26 2015-10-13 Google Inc. Contact lens employing optical signals for power and/or communication
US8857981B2 (en) 2012-07-26 2014-10-14 Google Inc. Facilitation of contact lenses with capacitive sensors
US9523865B2 (en) 2012-07-26 2016-12-20 Verily Life Sciences Llc Contact lenses with hybrid power sources
US9298020B1 (en) 2012-07-26 2016-03-29 Verily Life Sciences Llc Input system
US8919953B1 (en) 2012-08-02 2014-12-30 Google Inc. Actuatable contact lenses
US9696564B1 (en) 2012-08-21 2017-07-04 Verily Life Sciences Llc Contact lens with metal portion and polymer layer having indentations
US9111473B1 (en) 2012-08-24 2015-08-18 Google Inc. Input system
US9395468B2 (en) 2012-08-27 2016-07-19 Ocular Dynamics, Llc Contact lens with a hydrophilic layer
US8820934B1 (en) 2012-09-05 2014-09-02 Google Inc. Passive surface acoustic wave communication
US20140192315A1 (en) 2012-09-07 2014-07-10 Google Inc. In-situ tear sample collection and testing using a contact lens
US9398868B1 (en) 2012-09-11 2016-07-26 Verily Life Sciences Llc Cancellation of a baseline current signal via current subtraction within a linear relaxation oscillator-based current-to-frequency converter circuit
US10010270B2 (en) 2012-09-17 2018-07-03 Verily Life Sciences Llc Sensing system
US9326710B1 (en) 2012-09-20 2016-05-03 Verily Life Sciences Llc Contact lenses having sensors with adjustable sensitivity
US8870370B1 (en) 2012-09-24 2014-10-28 Google Inc. Contact lens that facilitates antenna communication via sensor impedance modulation
US8960898B1 (en) 2012-09-24 2015-02-24 Google Inc. Contact lens that restricts incoming light to the eye
US8989834B2 (en) 2012-09-25 2015-03-24 Google Inc. Wearable device
US20140088372A1 (en) 2012-09-25 2014-03-27 Google Inc. Information processing method
US8979271B2 (en) 2012-09-25 2015-03-17 Google Inc. Facilitation of temperature compensation for contact lens sensors and temperature sensing
US8985763B1 (en) 2012-09-26 2015-03-24 Google Inc. Contact lens having an uneven embedded substrate and method of manufacture
US8821811B2 (en) 2012-09-26 2014-09-02 Google Inc. In-vitro contact lens testing
US9884180B1 (en) 2012-09-26 2018-02-06 Verily Life Sciences Llc Power transducer for a retinal implant using a contact lens
US8960899B2 (en) 2012-09-26 2015-02-24 Google Inc. Assembling thin silicon chips on a contact lens
US9063351B1 (en) 2012-09-28 2015-06-23 Google Inc. Input detection system
US8965478B2 (en) 2012-10-12 2015-02-24 Google Inc. Microelectrodes in an ophthalmic electrochemical sensor
US9176332B1 (en) 2012-10-24 2015-11-03 Google Inc. Contact lens and method of manufacture to improve sensor sensitivity
US9757056B1 (en) 2012-10-26 2017-09-12 Verily Life Sciences Llc Over-molding of sensor apparatus in eye-mountable device
US8874182B2 (en) 2013-01-15 2014-10-28 Google Inc. Encapsulated electronics
US9289954B2 (en) 2013-01-17 2016-03-22 Verily Life Sciences Llc Method of ring-shaped structure placement in an eye-mountable device
US20140209481A1 (en) 2013-01-25 2014-07-31 Google Inc. Standby Biasing Of Electrochemical Sensor To Reduce Sensor Stabilization Time During Measurement
US9636016B1 (en) 2013-01-25 2017-05-02 Verily Life Sciences Llc Eye-mountable devices and methods for accurately placing a flexible ring containing electronics in eye-mountable devices
KR101524271B1 (en) * 2013-03-11 2015-05-29 (주) 개마텍 A composition of anti-fingerprint coating layer with a plurality of thin films and method of manufacturing the same.
US9161712B2 (en) 2013-03-26 2015-10-20 Google Inc. Systems and methods for encapsulating electronics in a mountable device
US9113829B2 (en) 2013-03-27 2015-08-25 Google Inc. Systems and methods for encapsulating electronics in a mountable device
US20140371560A1 (en) 2013-06-14 2014-12-18 Google Inc. Body-Mountable Devices and Methods for Embedding a Structure in a Body-Mountable Device
US9084561B2 (en) 2013-06-17 2015-07-21 Google Inc. Symmetrically arranged sensor electrodes in an ophthalmic electrochemical sensor
US9948895B1 (en) 2013-06-18 2018-04-17 Verily Life Sciences Llc Fully integrated pinhole camera for eye-mountable imaging system
US9685689B1 (en) 2013-06-27 2017-06-20 Verily Life Sciences Llc Fabrication methods for bio-compatible devices
US9814387B2 (en) 2013-06-28 2017-11-14 Verily Life Sciences, LLC Device identification
US9028772B2 (en) 2013-06-28 2015-05-12 Google Inc. Methods for forming a channel through a polymer layer using one or more photoresist layers
US9307901B1 (en) 2013-06-28 2016-04-12 Verily Life Sciences Llc Methods for leaving a channel in a polymer layer using a cross-linked polymer plug
US9492118B1 (en) 2013-06-28 2016-11-15 Life Sciences Llc Pre-treatment process for electrochemical amperometric sensor
CN105917270A (en) 2013-11-15 2016-08-31 视觉力学有限责任公司 Contact lens with a hydrophilic layer
US9572522B2 (en) 2013-12-20 2017-02-21 Verily Life Sciences Llc Tear fluid conductivity sensor
US9654674B1 (en) 2013-12-20 2017-05-16 Verily Life Sciences Llc Image sensor with a plurality of light channels
US9366570B1 (en) 2014-03-10 2016-06-14 Verily Life Sciences Llc Photodiode operable in photoconductive mode and photovoltaic mode
US9184698B1 (en) 2014-03-11 2015-11-10 Google Inc. Reference frequency from ambient light signal
US9789655B1 (en) 2014-03-14 2017-10-17 Verily Life Sciences Llc Methods for mold release of body-mountable devices including microelectronics
US10525170B2 (en) 2014-12-09 2020-01-07 Tangible Science, Llc Medical device coating with a biocompatible layer

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4055378A (en) * 1971-12-31 1977-10-25 Agfa-Gevaert Aktiengesellschaft Silicone contact lens with hydrophilic surface treatment
US4099859A (en) * 1974-12-02 1978-07-11 High Voltage Engineering Corporation Contact lens having a smooth surface layer of a hydrophilic polymer
US4311828A (en) * 1979-07-16 1982-01-19 Shin-Etsu Chemical Co., Ltd. Method for modifying surface properties of shaped articles of polymeric materials with low temperature plasma
GB2119957A (en) * 1982-04-29 1983-11-23 Agripat Sa Annealed polyvinyl alcohol contact lens
US4560458A (en) * 1983-01-31 1985-12-24 Shin-Etsu Chemical Co., Ltd. Method for improving surface properties of a shaped article of a synthetic resin
US4632842A (en) * 1985-06-20 1986-12-30 Atrium Medical Corporation Glow discharge process for producing implantable devices
US4718907A (en) * 1985-06-20 1988-01-12 Atrium Medical Corporation Vascular prosthesis having fluorinated coating with varying F/C ratio
US5002582A (en) * 1982-09-29 1991-03-26 Bio-Metric Systems, Inc. Preparation of polymeric surfaces via covalently attaching polymers
US5091204A (en) * 1985-08-23 1992-02-25 Weshington Research Foundation Polymeric intraocular lens material having improved surface properties

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2999056A (en) * 1956-10-04 1961-09-05 Du Pont Irradiation bonding of acidic compounds to shaped polymeric structures
US3228741A (en) * 1962-06-29 1966-01-11 Mueller Welt Contact Lenses In Corneal contact lens fabricated from transparent silicone rubber
US3925178A (en) * 1970-04-17 1975-12-09 Hymie D Gesser Contact lenses
US3761299A (en) * 1970-10-13 1973-09-25 Eastman Kodak Co Treating polymeric surfaces
US3959105A (en) * 1972-12-27 1976-05-25 Agfa-Gevaert, A.G. Process for the production of hydrophilic surfaces on silicon elastomer articles
US3880818A (en) * 1972-01-03 1975-04-29 Mitchel Shen Physiologically compatible plastic contact lenses and a method for their production
US4189364A (en) * 1972-05-12 1980-02-19 Hydroplastics, Inc. Method for preparing hydrophilic polymers and polymer grafts including irradiation
US3985697A (en) * 1972-10-18 1976-10-12 Uroptics International Incorporated Hydrophilic contact lens material
GB1463301A (en) * 1973-07-18 1977-02-02 Highgate D J Polymer properties
US4122942A (en) * 1974-01-31 1978-10-31 Wolfson Leonard G Hydrophilic contact lens case
US3944709A (en) * 1974-05-13 1976-03-16 Polaroid Corporation Surface modification by electrical discharge in a mixture of gases
CA1077787A (en) * 1975-11-21 1980-05-20 National Aeronautics And Space Administration Abrasion resistant coatings for plastic surfaces
US4143949A (en) * 1976-10-28 1979-03-13 Bausch & Lomb Incorporated Process for putting a hydrophilic coating on a hydrophobic contact lens
US4096315A (en) * 1976-12-15 1978-06-20 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Process for producing a well-adhered durable optical coating on an optical plastic substrate
US4131691A (en) * 1977-09-22 1978-12-26 Surface Activation Corporation Coating a substrate by glow discharge graft polymerization
US4123308A (en) * 1977-10-19 1978-10-31 Union Carbide Corporation Process for chemically bonding a poly-p-xylylene to a thermosetting resin and article produced thereby
DE2756114B1 (en) * 1977-12-16 1979-05-23 Titmus Eurocon Kontaktlinsen Process for the surface treatment of a hard or dehydrated hydrophilic contact lens
US4240163A (en) * 1979-01-31 1980-12-23 Galin Miles A Medicament coated intraocular lens
JPS56831A (en) * 1979-06-18 1981-01-07 Shin Etsu Chem Co Ltd Surface treatment of silicone resin molded product
US4277595A (en) * 1979-09-13 1981-07-07 Bausch & Lomb Incorporated Water absorbing contact lenses made from polysiloxane/acrylic acid polymer
US4312575A (en) * 1979-09-18 1982-01-26 Peyman Gholam A Soft corneal contact lens with tightly cross-linked polymer coating and method of making same
US4328257A (en) * 1979-11-26 1982-05-04 Electro-Plasma, Inc. System and method for plasma coating
DE3002664C2 (en) * 1980-01-25 1989-05-18 Titmus Eurocon Kontaktlinsen Gmbh & Co Kg, 8750 Aschaffenburg Soft contact lens
FR2483310A1 (en) * 1980-05-29 1981-12-04 Fibar Ste Civile Immob TREATMENT PROCESS FOR MAKING HYDROPHILIC CONTACT LENSES HYDROPHILIC
DE3116026C2 (en) * 1981-04-22 1983-12-01 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., 8000 München Method for producing a biocompatible layer on vascular prostheses and device for carrying out the method
US4430458A (en) * 1981-10-08 1984-02-07 Kelvin Lenses Limited Hydrogel-forming polymeric materials
US4405773A (en) * 1982-02-05 1983-09-20 Schering Corporation Hydrophylic contact lenses and methods for making same
US4478873A (en) * 1983-05-23 1984-10-23 American Optical Corporation Method imparting anti-static, anti-reflective properties to ophthalmic lenses
US4656083A (en) * 1983-08-01 1987-04-07 Washington Research Foundation Plasma gas discharge treatment for improving the biocompatibility of biomaterials
US4731080A (en) * 1985-01-18 1988-03-15 Galin Miles A Coated intraocular lens
US4919659A (en) * 1985-12-16 1990-04-24 The Board Of Regents For The University Of Washington Radio frequency plasma deposited polymers that enhance cell growth
US4720512A (en) * 1986-03-24 1988-01-19 Becton, Dickinson And Company Polymeric articles having enhanced antithrombogenic activity
FR2614317B1 (en) * 1987-04-22 1989-07-13 Air Liquide PROCESS FOR PROTECTING POLYMERIC SUBSTRATE BY PLASMA DEPOSITION OF COMPOUNDS OF THE SILICON OXYNITRIDE TYPE AND DEVICE FOR IMPLEMENTING SAME.
US4927676A (en) * 1988-07-01 1990-05-22 Becton, Dickinson And Company Method for rapid adherence of endothelial cells onto a surface and surfaces prepared thereby
US4865870A (en) * 1988-07-07 1989-09-12 Becton, Dickinson And Company Method for rendering a substrate surface antithrombogenic
US4885077A (en) * 1988-11-17 1989-12-05 Becton, Dickinson And Company Composite membrane, method for its preparation and electrolyte sensor including same
US5080924A (en) * 1989-04-24 1992-01-14 Drexel University Method of making biocompatible, surface modified materials
US5171267A (en) * 1989-08-31 1992-12-15 The Board Of Regents Of The University Of Washington Surface-modified self-passivating intraocular lenses
US5091240A (en) * 1989-09-05 1992-02-25 Tambrands, Inc. Laminate incorporating hot melt and water based adhesives
WO1992007464A1 (en) * 1990-10-24 1992-05-14 University Of Florida Combined plasma and gamma radiation polymerization method for modifying surfaces

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4055378A (en) * 1971-12-31 1977-10-25 Agfa-Gevaert Aktiengesellschaft Silicone contact lens with hydrophilic surface treatment
US4099859A (en) * 1974-12-02 1978-07-11 High Voltage Engineering Corporation Contact lens having a smooth surface layer of a hydrophilic polymer
US4311828A (en) * 1979-07-16 1982-01-19 Shin-Etsu Chemical Co., Ltd. Method for modifying surface properties of shaped articles of polymeric materials with low temperature plasma
GB2119957A (en) * 1982-04-29 1983-11-23 Agripat Sa Annealed polyvinyl alcohol contact lens
US5002582A (en) * 1982-09-29 1991-03-26 Bio-Metric Systems, Inc. Preparation of polymeric surfaces via covalently attaching polymers
US4560458A (en) * 1983-01-31 1985-12-24 Shin-Etsu Chemical Co., Ltd. Method for improving surface properties of a shaped article of a synthetic resin
US4632842A (en) * 1985-06-20 1986-12-30 Atrium Medical Corporation Glow discharge process for producing implantable devices
US4718907A (en) * 1985-06-20 1988-01-12 Atrium Medical Corporation Vascular prosthesis having fluorinated coating with varying F/C ratio
US5091204A (en) * 1985-08-23 1992-02-25 Weshington Research Foundation Polymeric intraocular lens material having improved surface properties

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0668798A4 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005023018A1 (en) * 2005-05-19 2006-11-23 Rehau Ag + Co. Modification of silicone rubber objects to produce a non-stick surface, e.g. on tubing for catheters or other medical uses, involves depositing a silicate-containing functional layer on the surface from a flame
WO2006122744A1 (en) 2005-05-19 2006-11-23 Rehau Ag + Co Method for modifying a silicone rubber surface
DE102005023017A1 (en) * 2005-05-19 2006-11-23 Rehau Ag + Co Silicone rubber objects with a non-stick surface, e.g. tubing for catheters or other medical uses, obtained by modifying the surface with a silicate-containing functional layer formed by deposition from a flame
EP2335917A1 (en) * 2008-09-26 2011-06-22 National University Corporation Tokyo Medical and Dental University Polymer brush composite and method for producing same
EP2335917A4 (en) * 2008-09-26 2012-08-01 Nat Univ Corp Tokyo Med & Dent Polymer brush composite and method for producing same
US8974054B2 (en) 2012-02-01 2015-03-10 Lenswista Ag Contact lens

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JPH08505295A (en) 1996-06-11
AU5845394A (en) 1994-06-08
US5326584A (en) 1994-07-05
EP0668798A4 (en) 1998-08-05

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