(19)
(11)EP 3 083 216 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
31.01.2018 Bulletin 2018/05

(21)Application number: 14830754.9

(22)Date of filing:  16.12.2014
(51)International Patent Classification (IPC): 
B29D 11/00(2006.01)
G02B 1/04(2006.01)
(86)International application number:
PCT/US2014/070539
(87)International publication number:
WO 2015/095157 (25.06.2015 Gazette  2015/25)

(54)

A SILICONE HYDROGEL LENS WITH A CROSSLINKED HYDROPHILIC COATING

SILIKONHYDROGELLINSE MIT VERNETZTER HYDROPHILER BESCHICHTUNG

LENTILLE EN HYDROGEL DE SILICONE AVEC REVÊTEMENT HYDROPHILE RÉTICULÉ


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 17.12.2013 US 201361916879 P

(43)Date of publication of application:
26.10.2016 Bulletin 2016/43

(73)Proprietor: Novartis AG
4056 Basel (CH)

(72)Inventor:
  • QIU, Yongxing
    Suwanee, GA 30024 (US)

(74)Representative: Bohest AG 
Holbeinstrasse 36-38
4051 Basel
4051 Basel (CH)


(56)References cited: : 
US-A1- 2012 026 457
  
      
    Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


    Description


    [0001] The present invention generally relates to a cost-effective and time-efficient method for applying a crosslinked hydrophilic coating onto a silicone hydrogel contact lens to reduce its positively charged preservatives such as PHMB uptake and to improve its hydrophilicity and lubricity.

    BACKGROUND



    [0002] In recent years, soft silicone hydrogel contact lenses, for example, Focus NIGHT & DAY™ and AIROPTIX™ (CIBA VISION), and PureVision™(Bausch & Lomb) become more and more popular because of their high oxygen permeability and comfort. "Soft" contact lenses conform closely to the shape of the eye, so oxygen cannot easily circumvent the lens. Soft contact lenses must allow oxygen from the surrounding air (i.e., oxygen) to reach the cornea because the cornea does not receive oxygen from the blood supply like other tissue. If sufficient oxygen does not reach the cornea, corneal swelling occurs. Extended periods of oxygen deprivation cause the undesirable growth of blood vessels in the cornea. By having high oxygen permeability, a silicone hydrogel contact lens allows sufficient oxygen permeate through the lens to the cornea and to have minimal adverse effects on corneal health.

    [0003] However, a silicone hydrogel material typically has a surface or at least some areas of its surface which is hydrophobic (non-wettable). Lipids or proteins from the ocular environment can be adsorbed onto hydrophobic surface or surface areas of a silicone hydrogel contact lens. The hydrophobic surface or surface areas of a silicone hydrogel contact lens may cause it be adhered to the eye. Thus, a silicone hydrogel contact lens will generally require a surface modification to increase surface hydrophilicity.

    [0004] A known method for modifying the hydrophilicity of a relatively hydrophobic contact lens material is to attach hydrophilic polymers onto contact lenses according to various mechanisms (see for example, US Patent No. 6,099,122, 6,436,481, 6,440,571, 6,447,920, 6,465,056, 6,521,352, 6,586,038, 6,623,747, 6,730,366, 6,734,321, 6,835,410, 6,878,399, 6,923,978, 6,440,571, and 6,500,481, US Patent Application Publication Nos. 2009/0145086 A1, 2009/0145091A1, 2008/0142038A1, and 2007/0122540A1. Although those techniques can be used in rendering a silicone hydrogel material wettable, they may not be cost-effective and/or time-efficient for implementation in a mass production environment, because they typically require relatively long time and/or involve laborious, multiple steps to obtain a hydrophilic coating.

    [0005] The amino groups and or carboxyl groups introduced on and or the surface of silicone hydrogel contact lens render the lenses hydrophilic, i.e. they wet easily and absorb water and also contribute to lens hydrophilic character. With water absorption, the lenses also may take up chemicals dissolved in the water. When contact lens care products containing compounds bearing positive charges are used with the contact lenses, an ionic interaction can take place between the contact lenses and those components. Use of products containing such components can produce undesirable clinical symptoms in some persons, such as diffuse corneal staining and product intolerance.

    [0006] The most common preservatives and disinfecting agents known are Polyhexamethylenebiguanide (PHMB), polymeric quaternary ammonium compound such as Polyquaternium-1® and other positively charged preservatives. It was found that many of these preservatives and disinfecting agents become concentrated in the lenses to a sufficient degree that when the lens is placed in the aqueous environment of the eye, the preservatives or disinfectants are released from the lens and cause eye irritation. This problem was found to be particularly severe with positively charged preservatives or disinfecting components.

    [0007] Therefore, there is a need for a cost-effective and time-efficient method for reducing hydrophilic silicone hydrogel contact lens' positively charged preservatives such as PHMB uptake. There is still a need for a cost-effective and time-efficient method of applying a crosslinked hydrophilic coating onto a silicone hydrogel contact lens to reduce its positively charged preservatives such as PHMB uptake and to improve its hydrophilicity and lubricity. In addition, the present invention provides an ophthalmic lens product

    SUMMARY OF THE INVENTION



    [0008] The invention, in one aspect, provides a method for producing silicone hydrogel contact lenses with crosslinked hydrophilic coatings thereon, comprising the steps of:
    1. (a) obtaining a silicone hydrogel contact lens having amino groups and/or carboxyl groups on and/or near its surface and a water-soluble and thermally-crosslinkable hydrophilic polymeric material, wherein the silicone hydrogel contact lens comprises amino groups or carboxyl groups or both on and/or near the surface of the contact lens, wherein the hydrophilic polymeric material comprises (i) from about 20% to about 95%, preferably from about 35% to about 90%, more preferably from about 50% to about 85%, by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80%, preferably from about 10% to about 65%, even more preferably from about 15% to about 50%, by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof, and (iii) positively-charged azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains through one or more covalent linkages each formed between one azetitdinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and
    2. (b) heating the silicone hydrogel contact lens immersed in an in-packing-coating packaging solution comprising the hydrophilic polymeric material and at least one buffering agent in an amount sufficient to maintain a pH of from about 6.0 to about 8.5 and has a tonicity of from about 200 to about 450 milliosmol (mOsm) and a viscosity of from about 1 centipoise to about 20 centipoises at 25°C in a lens package to and at a temperature from about 40°C to about 140°C, preferably from about 60°C to about 120°C, even more preferably from about 75°C to about 95°C, most preferably from about 80°C to about 90°C, for a period of time sufficient to covalently attach the hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through second covalent linkages each formed between one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and/or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens,
    3. (c) adding a polyazetidinium groups-containing component into the in-packing-coating solution with the silicone contact lens of the step (b), wherein the polyazetidinium groups-containing component comprise at least two groups selected from the group consisting of Formula (II), Formula (III) and mixtures thereof:



      wherein: R1 and R2 are independently an alkylene group containing 1 to 6 carbon atoms; X is an anionic counterion; Y1, Y2 and Y3 are each independently selected from the group consisting of hydrogen, hydroxyl, halo, alkoxy, alkyl, amino, carboxy, acetoxy, cyano and sulfhydryl; and Y4 is a chain-terminating group, selected from the group consisting of hydrogen, alkyl, alkoxy and acyloxy;
    4. (d) sealing the lens package with the contact lens and the in-packing-coating solution of step (c)
    5. (e) reducing the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens by autoclaving the package with the contact lens and the in-package-coating solution therein of step (d) and inducing reaction between azetidinium groups of the polyazetidinium groups-containing component and residual amino groups and/or carboxyl groups remained on and/or the surface of the silicone hydrogel contact lens immersed in the in-package-coating solution, wherein the reduction of the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens of step (e) is characterized by having an decreased positively charged preservatives uptake in relation to the silicone hydrogel contact lens of step (b) by at least 20%.


    [0009] These and other aspects of the invention will become apparent from the following description of the presently preferred embodiments. The detailed description is merely illustrative of the invention and does not limit the scope of the invention, which is defined by the appended claims and equivalents thereof. As would be obvious to one skilled in the art, many variations and modifications of the invention may be affected without departing from the spirit and scope of the novel concepts of the disclosure.

    DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION



    [0010] A "silicone hydrogel contact lens" refers to a contact lens comprising a silicone hydrogel material. A "silicone hydrogel" refers to a silicone-containing polymeric material which can absorb at least 10 percent by weight of water when it is fully hydrated and is obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinylic monomer or at least one silicone-containing vinylic macromer or at least one silicone-containing prepolymer having ethylenically unsaturated groups.

    [0011] A "vinylic monomer", as used herein, refers to a low molecular weight compound that has an ethylenically unsaturated group and can be polymerized actinically or thermally. Low molecular weight typically means average molecular weights less than 700 Daltons.

    [0012] The term "olefinically unsaturated group" or "ethylenically unsaturated group" is employed herein in a broad sense and is intended to encompass any groups containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include without limitation (meth)acryloyl methacryloyl

    allyl, vinyl

    styrenyl, or other C=C containing groups.

    [0013] The term "(meth)acrylamide" refers to methacrylamide and/or acrylamide.

    [0014] The term "(meth)acrylate" refers to methacrylate and/or acrylate.

    [0015] A "hydrophilic vinylic monomer", as used herein, refers to a vinylic monomer which as a homopolymer typically yields a polymer that is water-soluble or can absorb at least 10 percent by weight water.

    [0016] A "hydrophobic vinylic monomer", as used herein, refers to a vinylic monomer which as a homopolymer typically yields a polymer that is insoluble in water and can absorb less than 10 percent by weight water.

    [0017] A "macromer" or "prepolymer" refers to a medium and high molecular weight compound or polymer that contains ethylenically unsaturated groups. Medium and high molecular weight typically means average molecular weights greater than 700 Daltons.

    [0018] A "polymer" means a material formed by polymerizing/crosslinking one or more monomers or macromers or prepolymers.

    [0019] "Molecular weight" of a polymeric material (including monomeric or macromeric materials), as used herein, refers to the weight-average molecular weight unless otherwise specifically noted or unless testing conditions indicate otherwise.

    [0020] The term "amino group" refers to a primary or secondary amino group of formula - NHR', where R' is hydrogen or a C1-C20 unsubstituted or substituted, linear or branched alkyl group, unless otherwise specifically noted.

    [0021] An "epichlorohydrin-functionalized polyamine" or "epichlorohydrin-functionalized polyamidoamine" refers to a polymer obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a substantial percentage of amine groups of the polyamine or polyamidoamine into azetidinium groups.

    [0022] An "azetidinium group" refers to a positively charged group of



    [0023] The term "thermally-crosslinkable" in reference to a polymeric material or a functional group means that the polymeric material or the functional group can undergo a crosslinking (or coupling) reaction with another material or functional group at a relatively-elevated temperature (from about 40°C to about 140°C), whereas the polymeric material or functional group cannot undergo the same crosslinking reaction (or coupling reaction) with another material or functional group at room temperature (i.e., from about 22°C to about 28°C, preferably from about 24°C to about 26°C, in particular at about 25°C) to an extend detectable for a period of about one hour.

    [0024] The term "reactive vinylic monomer" refers to a vinylic monomer having a carboxyl group or an amino group (i.e., a primary or secondary amino group).

    [0025] The term "non-reactive hydrophilic vinylic monomer" refers to a hydrophilic vinylic monomer which is free of any carboxyl group or amino group (i.e., primary or secondary amino group). A non-reactive vinylic monomer can include a tertiary or quaternium amino group.

    [0026] The term" a polyazetidinium groups-containing component" refers to a polymer comprises at least two groups selected from the group consisting of Formula (II), Formula (III) and mixtures thereof:



    wherein: R1 and R2 are independently an alkylene group containing 1 to 6 carbon atoms; X is an anionic counterion; Y1, Y2 and Y3 are each independently selected from the group consisting of hydrogen, hydroxyl, halo, alkoxy, alkyl, amino, carboxy, acetoxy, cyano and sulfhydryl; and Y4 is a chain-terminating group, selected from the group consisting of hydrogen, alkyl, alkoxy and acyloxy.

    [0027] The term "water-soluble" in reference to a polymer means that the polymer can be dissolved in water to an extent sufficient to form an aqueous solution of the polymer having a concentration of up to about 30% by weight at room temperature (defined above).

    [0028] A "water contact angle" refers to an average water contact angle (i.e., contact angles measured by Sessile Drop method), which is obtained by averaging measurements of contact angles with at least 3 individual contact lenses.

    [0029] The invention is generally directed to a cost-effective and time-efficient method for applying a crosslinked hydrophilic coating onto a silicone hydrogel contact lens to reduce its positively charged preservatives such as PHMB uptake and to improve its hydrophilicity.

    [0030] The invention is partly based on the discoveries that a water-soluble, azetidinium-containing, and thermally-crosslinkable hydrophilic polymeric material, which is a polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin derivative, can be used to form a crosslinked coating with a good surface hydrophilicity and/or wettability, a good hydrophilicity and a good intactness on a silicone hydrogel contact lens. At a relatively elevated temperature (defined above), positively-charged azetidinium groups react with functional groups such as amino groups, thiol groups, and carboxylate ion -COO- (i.e., the deprotonated form of a carboxyl group) to form neutral, hydroxyl-containing covalent linkages as illustrated in the scheme I

    in which R is the rest portion of a compound, L is -NR'- in which R' is hydrogen, a C1-C20 unsubstituted or substituted, linear or branched alkyl group or a polymer chain -S-, or-OC(=O)-. Because of the thermally-controllable reactivity of azetidinium groups, polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin (PAE) has been widely used as a wet-strengthening agent. However, PAE has not been successfully used to form crosslinked coatings on contact lenses, probably because crosslinked PAE coatings may not be able to impart desirable hydrophilicity/wettability to contact lenses. It is discovered here that PAE can be chemically-modified with a hydrophilicity-enhancing agent (especially a hydrophilic polymer) having one or more functional groups each capable of reacting with one azetidinium group, to obtain a water-soluble, azetidinium-containing polymeric material. Such polymeric material, which is still thermally-crosslinkable (reactive) due to the presence of azetidinium groups, can be used to form a crosslinked coating on a silicone hydrogel contact lens having reactive functional groups (e.g., amino groups, carboxyl groups, thiol groups, or combinations thereof) on and/or near its surface. And, the resultant coating on the contact lens has an improved surface hydrophilicity and/or wettability relative to a control coating obtained by using an unmodified (original or starting) PAE.

    [0031] It is believed that a hydrophilicity-enhancing agent may play at least two roles in increasing resultant crosslinked coatings: adding hydrophilic polymer chains onto a polyamine or polyamidoamine polymer chain to form a highly-branched hydrophilic polymeric material with dangling polymer chains and/or chain segments; and decreasing the crosslinking density of the crosslinked coating by reducing significantly the number of azetidinium groups of the crosslinkable polymeric material (coating material). A coating with a loose structure and dangling polymer chains and/or chain segments is believed to impart a good surface hydrophilicity and wettability.

    [0032] The invention is also partly based on the discoveries that a crosslinked coating of the invention can be advantageously formed onto a silicone hydrogel contact lens directly in a lens package containing the contact lens immersed in a lens packaging solution in the presence of a water-soluble azetidinium-containing polymeric material. The presence of the azetidinium-containing polymeric material can be accomplished either by adding the azetidinium-containing polymeric material in the lens packaging solution, or by, prior to packaging, depositing physically a layer of the azetidinium-containing polymeric material onto the surface of a contact lens at room temperature.

    [0033] Typically, contact lenses, which are hydrated and packaged in a packaging solution, must be sterilized. Sterilization of the hydrated lenses during manufacturing and packaging is typically accomplished by autoclaving. The autoclaving process involves heating the packaging of a contact lens to a temperature of from about 118°C to about 125°C for approximately 20-40 minutes under pressure.

    [0034] The invention is further partly based on the discoveries that an in- package- coating process with two heating steps can be used to reduce the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens while the silicone hydrogel contact lens still maintains its surface hydrophilicity (or wettability) measured by Sessile Drop. The reduction of the concentration carboxyl groups on and/or near the silicone hydrogel contact lens is characterized by having a decreased positively charged preservatives uptake relative to the silicone hydrogel contact lens without addition of polyamidoamine epichlorohydrin into the package solution during autoclaving. During the first heating step, the silicone hydrogel contact lens in an aqueous solution is heated in the presence of the hydrophilic polymeric material to and at a temperature from about 40°C to about 140°C for a period of time sufficient to covalently attach the hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through covalent linkages each formed between one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and/or near the surface of the contact lens to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens. The silicone hydrogel contact lens with the crosslinked hydrophilic coating has a surface wettability characterized by having an averaged water contact angle of about 90 degrees or less. However, the resulting silicone hydrogel contact lens with the crosslinked hydrophilic coating may have a high residual charge, for example, carboxyl groups which is introduced on and/or the surface of silicone hydrogel contact lens during the crosslinked hydrophilic coating process. This process is disclosed in commonly assigned U.S. patent. During the second heating step, reaction between azetidinium groups of the polyazetidinium groups-containing component introduced for this second heating step and residual amino groups and/or carboxyl groups remained on and/or the surface of the silicone hydrogel contact lens immersed in the in-package-coating solution, after the second heating step, reduce the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens. The reduction of negative charge is characterized by having a decreased positively charged preservatives uptake in relation to the silicone hydrogel contact lens of without second heating process by at least 20%.

    [0035] The first and second heating step may have the same temperature such as autoclaving process temperature. However, it is preferably the first heating temperature is lower than 100 degree centigrade to avoid the expensive high pressure heating process.

    [0036] The invention, in one aspect, provides a method for producing silicone hydrogel contact lenses with crosslinked hydrophilic coatings thereon, comprising the steps of:
    1. (a) obtaining a silicone hydrogel contact lens having amino groups and/or carboxyl groups on and/or near its surface and a water-soluble and thermally-crosslinkable hydrophilic polymeric material, wherein the silicone hydrogel contact lens comprises amino groups or carboxyl groups or both on and/or near the surface of the contact lens, wherein the hydrophilic polymeric material comprises (i) from about 20% to about 95%, preferably from about 35% to about 90%, more preferably from about 50% to about 85%, by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80%, preferably from about 10% to about 65%, even more preferably from about 15% to about 50%, by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof, and (iii) positively-charged azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains through one or more covalent linkages each formed between one azetitdinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and
    2. (b) heating the silicone hydrogel contact lens immersed in a packaging solution comprising the hydrophilic polymeric material and at least one buffering agent in an amount sufficient to maintain a pH of from about 6.0 to about 8.5 and has a tonicity of from about 200 to about 450 milliosmol (mOsm) and a viscosity of from about 1 centipoise to about 20 centipoises at 25°C in a lens package to and at a temperature from about 40°C to about 140°C, preferably from about 60°C to about 120°C, even more preferably from about 75°C to about 95°C, most preferably from about 80°C to about 90°C, for a period of time sufficient to covalently attach the hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through second covalent linkages each formed between one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and/or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens,
    3. (c) adding a polyazetidinium groups-containing component into the package solution with the silicone contact lens of the step (b), wherein the polyazetidinium groups-containing component comprise at least two groups selected from the group consisting of Formula (II), Formula (III) and mixtures thereof:

      wherein: R1 and R2 are independently an alkylene group containing 1 to 6 carbon atoms; X is an anionic counterion; Y1, Y2 and Y3 are each independently selected



      from the group consisting of hydrogen, hydroxyl, halo, alkoxy, alkyl, amino, carboxy, acetoxy, cyano and sulfhydryl; and Y4 is a chain-terminating group, selected from the group consisting of hydrogen, alkyl, alkoxy and acyloxy;

    4. (d) sealing the lens package with the contact lens and the package solution of step (c)
    5. (e) reducing the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens by autoclaving the package with the contact lens and the in-package-coating solution therein of step (d) and inducing reaction between azetidinium groups of the polyazetidinium groups-containing component and residual amino groups and/or carboxyl groups remained on and/or the surface of the silicone hydrogel contact lens immersed in the in-package-coating solution, wherein the reduction of the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens of step (e) is characterized by having an decreased positively charged preservatives uptake in relation to the silicone hydrogel contact lens of step (b) by at least 20%.
      A person skilled in the art knows very well how to make contact lenses. For example, contact lenses can be produced in a conventional "spin-casting mold," as described for example in U.S. Patent No. 3,408,429, or by the full cast-molding process in a static form, as described in U.S. Patent Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810. In cast-molding, a lens formulation typically is dispensed into molds and cured (i.e., polymerized and/or crosslinked) in molds for making contact lenses. For production of silicone hydrogel contact lenses, a lens formulation for cast-molding generally comprises at least one components selected from the group consisting of a silicone-containing vinylic monomer, a silicone-containing vinylic macromer, a silicone-containing prepolymer, a hydrophilic vinylic monomer, a hydrophilic vinylic macromer, a hydrophobic vinylic monomer, and combination thereof, as well known to a person skilled in the art. A silicone hydrogel contact lens formulation can also comprise other necessary components known to a person skilled in the art, such as, for example, a crosslinking agent, a UV-absorbing agent, a visibility tinting agent (e.g., dyes, pigments, or mixtures thereof), antimicrobial agents (e.g., preferably silver nanoparticles), a bioactive agent, leachable lubricants, leachable tear-stabilizing agents, and mixtures thereof, as known to a person skilled in the art. Molded silicone hydrogel contact lenses then can be subjected to extraction with an extraction solvent to remove unpolymerized components from the molded lenses and to hydration process, as known by a person skilled in the art. Numerous silicone hydrogel lens formulations have been described in numerous patents and patent applications published by the filing date of this application.


    [0037] In accordance with the invention, a silicone hydrogel contact lens can either inherently comprise or be modified to comprise amino groups and/or carboxyl groups on and/or near its surface.

    [0038] Where a silicone hydrogel contact lens inherently comprises amino groups and/or carboxyl groups on and/or near its surface, it is obtained by polymerizing a silicone hydrogel lens formulation comprising a reactive vinylic monomer.

    [0039] Preferably, the silicone hydrogel contact lens is made from a lens formulation without limitation comprising at least one reactive vinylic monomer selected from the group consisting of amino-C2-C6 alkyl (meth)acrylate, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylate, allylamine, vinylamine, amino-C1-C6 alkyl (meth)acrylamide, C1-C6 alkylamino-C2-C6 alkyl (meth)acrylamide, acrylic acid, C1-C6 alkylacrylic acid, N,N-2-acrylamidoglycolic acid, and combinations thereof. The lens formulation comprises preferably from about 0.1 % to about 10%, more preferably from about 0.25% to about 7%, even more preferably from about 0.5% to about 5%, most preferably from about 0.75% to about 3%, by weight of the reactive vinylic monomer.

    [0040] A silicone hydrogel contact lens can also be subjected either to a surface treatment to form a reactive base coating having amino groups and/or carboxyl groups on the surface of the contact lens. Examples of surface treatments include without limitation a surface treatment by energy (e.g., a plasma, a static electrical charge, irradiation, or other energy source), chemical treatments, chemical vapor deposition, the grafting of hydrophilic vinylic monomers or macromers onto the surface of an article, layer-by-layer coating ("LbL coating"). "LbL coating", as used herein, refers to a coating that is not covalently attached to the polymer matrix of a contact lens and is obtained through a layer-by-layer ("LbL") deposition of charged or chargeable (by protonation or deprotonation) and/or non-charged materials on the lens. An LbL coating can be composed of one or more layers.

    [0041] Preferably, the surface treatment is an LbL coating process. In this preferred embodiment (i.e., the reactive LbL base coating embodiment), a resultant silicone hydrogel contact lens comprises a reactive LbL base coating including at least one layer of a reactive polymer (i.e., a polymer having pendant amino groups and/or carboxyl groups), wherein the reactive LbL base coating is obtained by contacting the contact lens with a solution of a reactive polymer. Contacting of a contact lens with a coating solution of a reactive polymer can occur by dipping it into the coating solution or by spraying it with the coating solution. One contacting process involves solely dipping the contact lens in a bath of a coating solution for a period of time or alternatively dipping the contact lens sequentially in a series of bath of coating solutions for a fixed shorter time period for each bath. Another contacting process involves solely spray a coating solution. However, a number of alternatives involve various combinations of spraying- and dipping- steps may be designed by a person having ordinary skill in the art. The contacting time of a contact lens with a coating solution of a reactive polymer may last up to about 10 minutes, preferably from about 5 to about 360 seconds, more preferably from about 5 to about 250 seconds, even more preferably from about 5 to about 200 seconds.

    [0042] In accordance with this reactive LbL base coating embodiment, the reactive polymer can be a linear or branched polymer having pendant amino groups and/or carboxyl groups. Any polymers having pendant amino groups and/or carboxyl groups can be used as a reactive polymer for forming base coatings on silicone hydrogel contact lenses. Examples of such reactive polymers include without limitation: a homopolymer of a reactive vinylic monomer; a copolymer of two or more reactive vinylic monomers; a copolymer of a reactive vinylic monomer with one or more non-reactive hydrophilic vinylic monomers (i.e., hydrophilic vinylic monomers free of any carboxyl or (primary or secondary) amino group); polyethyleneimine (PEI); polyvinylalcohol with pendant amino groups; a carboxyl-containing cellulose (e.g., carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose); hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); and combinations thereof.

    [0043] Preferred reactive vinylic monomers are those described previously, with carboxylic acid-containing vinylic monomers as most preferred reactive vinylic monomers for preparing reactive polymers for forming a reactive LbL base coating.

    [0044] Preferred examples of non-reactive hydrophilic vinylic monomers free of carboxyl or amino group include without limitation acrylamide (AAm), methacrylamide N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate (DMAEM), N,N-dimethylaminoethylacrylate (DMAEA), N,N-dimethylaminopropylmethacrylamide (DMAPMAm), and those described in US patent No. 5,461,433, and combinations thereof.

    [0045] Preferably, the reactive polymers for forming a reactive LbL base coating are polyacrylic acid, polymethacrylic acid, poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinylacetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylamine homo- or copolymer, or combinations thereof.

    [0046] The weight average molecular weight Mw of a reactive polymer for forming a reactive LbL base coating is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, more preferably at least about 100,000 Daltons, even more preferably from about 10,000 to 1,000,000 Daltons.

    [0047] A solution of a reactive polymer for forming a reactive LbL base coating on contact lenses can be prepared by dissolving one or more reactive polymers in water, a mixture of water and an organic solvent miscible with water, an organic solvent, or a mixture of one or more organic solvent. Preferably, the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvent. It is believed that a solvent system containing at least one organic solvent can swell a silicone hydrogel contact lens so that a portion of the reactive polymer may penetrate into the silicone hydrogel contact lens and increase the durability of the reactive base coating. Any organic solvents can be used in preparation of a solution of the reactive polymer.

    [0048] In another preferred embodiment, a silicone hydrogel comprises inherently amino groups and/or carboxyl groups on and/or near its surface and is further subjected to a surface treatment to form a reactive LbL base coating having amino groups and/or carboxyl groups therein.

    [0049] In accordance with the invention, a water-soluble and thermally-crosslinkable hydrophilic polymeric material containing azetidinium groups comprises (i.e., has a composition including) from about 20% to about 95%, preferably from about 35% to about 90%, more preferably from about 50% to about 85%, by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine and from about 5% to about 80%, preferably from about 10% to about 65%, even more preferably from about 15% to about 50%, by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof. The composition of the hydrophilic polymeric material is determined by the composition (based on the total weight of the reactants) of a reactants mixture used for preparing the thermally-crosslinkable hydrophilic polymeric material according to the crosslinking reactions shown in Scheme I above. For example, if a reactant mixture comprises about 75% by weight of an epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% by weight of at least one hydrophilicity-enhancing agent based on the total weight of the reactants, then the resultant hydrophilic polymeric material comprise about 75% by weight of first polymer chains derived from the epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% by weight of hydrophilic moieties or second polymer chains derived from said at least one hydrophilicity-enhancing agent. The azetidinium groups of the thermally-crosslinkable hydrophilic polymeric material are those azetidinium groups (of the epichlorohydrin-functionalized polyamine or polyamidoamine) which do not participate in crosslinking reactions for preparing the thermally-crosslinkable hydrophilic polymeric material.

    [0050] An epichlorohydrin-functionalized polyamine or polyamidoamine can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing primary or secondary amino groups. For example, a poly(alkylene imines) or a poly(amidoamine) which is a polycondensate derived from a polyamine and a dicarboxylic acid (e.g., adipic acid-diethylenetriamine copolymers) can react with epichlorohydrin to form an epichlorohydrin-functionalized polymer. Similarly, a homopolymer or copolymer of aminoalkyl(meth)acrylate, mono-alkylaminoalkyl (meth)acrylate, aminoalkyl(meth)acrylamide, or mono-alkylaminoalkyl (meth)acrylamide can also react with epichlorohydrin to form an epichlorohydrin-functionalized polyamine. The reaction conditions for epichlorohydrin-functionalization of a polyamine or polyamidoamine polymer are taught in EP1465931. A preferred epichlorohydrin-functionalized polymer is polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), such as, for example, Kymene® or Polycup® resins (epichlorohydrin-functionalized adipic acid-diethylenetriamine copolymers) from Hercules or Polycup® or Servamine® resins from Servo/Delden.

    [0051] Any suitable hydrophilicity-enhancing agents can be used in the invention so long as they contain at least one amino group, at least one carboxyl group, and/or at least one thiol group.

    [0052] A preferred class of hydrophilicity-enhancing agents include without limitation: amino-, carboxyl- or thiol-containing monosaccharides (e.g., 3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosaminic acid, mannosamine, saccharic acid 1,4-lactone, saccharide acid, Ketodeoxynonulosonic acid, N-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide); amino-, carboxyl- or thiol-containing disaccharides (e.g., chondroitin disaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, Lactobionic acid); and amino-, carboxyl- or thiol-containing oligosaccharides (e.g., carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); and combinations thereof.

    [0053] Another preferred class of hydrophilicity-enhancing agents is hydrophilic polymers having one or more amino, carboxyl and/or thiol groups. More preferably, the content of the amino (-NHR' with R' as defined above), carboxyl (-COOH) and/or thiol (-SH) groups in a hydrophilic polymer as a hydrophilicity-enhancing agent is less than about 40%, preferably less than about 30%, more preferably less than about 20%, even more preferably less than about 10%, by weight based on the total weight of the hydrophilic polymer.

    [0054] One preferred class of hydrophilic polymers as hydrophilicity-enhancing agents are amino- or carboxyl-containing polysaccharides, for example, such as, carboxymethylcellulose (having a carboxyl content of about 40% or less, which is estimated based on the composition of repeating units, -[C6H10-mO5(CH2CO2H)m]- in which m is 1 to 3), carboxyethylcellulose (having a carboxyl content of about 36% or less, which is estimated based on the composition of repeating units, -[C6H10-mO5(C2H4CO2H)m]- in which m is 1 to 3) carboxypropylcellulose (having a carboxyl content of about 32% or less, which is estimated based on the composition of repeating units, -[C6H10-mO5(C3H6CO2H)m]-, in which m is 1 to 3), hyaluronic acid (having a carboxyl content of about 11%, which is estimated based on the composition of repeating units, -(C13H20O9NCO2H)-), chondroitin sulfate (having a carboxyl content of about 9.8%, which is estimated based on the composition of repeating units, -(C12H18O13NS CO2H)-), or combinations thereof.

    [0055] Another preferred class of hydrophilic polymers as hydrophilicity-enhancing agents include without limitation: poly(ethylene glycol) (PEG) with mono-amino, carboxyl or thiol group (e.g., PEG-NH2, PEG-SH, PEG-COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a diamino- or dicarboxyl-terminated homo- or co-polymer of a non-reactive hydrophilic vinylic monomer; a monoamino- or monocarboxyl-terminated homo- or co-polymer of a non-reactive hydrophilic vinylic monomer; a copolymer which is a polymerization product of a composition comprising (1) about 60% by weight or less, preferably from about 0.1 % to about 30%, more preferably from about 0.5% to about 20%, even more preferably from about 1 % to about 15%, by weight of one or more reactive vinylic monomers and (2) at least one non-reactive hydrophilic vinylic monomer; and combinations thereof. Reactive vinylic monomer(s) and non-reactive hydrophilic vinylic monomer(s) are those described previously.

    [0056] More preferably, a hydrophilic polymer as a hydrophilicity-enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; multi-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer selected from the group consisting of acryamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl (metha)crylamide, (meth)acryloyloxyethyl phosphorylcholine, and combinations thereof; a copolymer which is a polymerization product of a composition comprising (1) from about 0.1 % to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1 % to about 15%, by weight of (meth)acrylic acid, allylamine and/or amino-C2-C4 alkyl (meth)acrylate, and (2) at least one non-reactive hydrophilic vinylic monomer selected from the group consisting of acryamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, (meth)acryloyloxyethyl phosphorylcholine, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, and combination thereof.

    [0057] Most preferably, the hydrophilicity-enhancing agent as a hydrophilicity-enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated polyvinylpyrrolidone; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated polyacrylamide; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA); monoamino- or monocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(NVP-co-N,N-dimethylaminoethyl (meth)acrylate)); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(vinylalcohol); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly[(meth)acryloyloxyethyl phosphrylcholine] homopolymer or copolymer; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(NVP-co-vinyl alcohol); monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly[(meth)acrylic acid-co-acrylamide] with from about 0.1 % to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1 % to about 15%, by weight of (meth)acrylic acid; poly[(meth)acrylic acid-co-NVP) with from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15%, by weight of (meth)acrylic acid; a copolymer which is a polymerization product of a composition comprising (1) (meth)acryloyloxyethyl phosphorylcholine and (2) from about 0.1 % to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1 % to about 15%, by weight of (meth)acrylic acid, allylamine and/or amino-C2-C4alkyl (meth)acrylate; and combination thereof.

    [0058] PEGs with functional groups and multi-arm PEGs with functional groups can be obtained from various commercial suppliers, e.g., Polyscience, and Shearwater Polymers, inc., etc.

    [0059] Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymers of one or more non-reactive hydrophilic vinylic monomers or of a phosphorylcholine-containing vinylic monomer can be prepared according to procedures described in U.S. Patent No. 6,218,508. For example, to prepare a diamino- or dicarboxyl-terminated homo- or co-polymer of a non-reactive hydrophilic vinylic monomer, the non-reactive vinylic monomer, a chain transfer agent with an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptanes, aminomercaptans, or carboxyl-containing mercaptanes) and optionaly other vinylic monomer are copolymerized (thermally or actinically) with a reactive vinylic monomer (having an amino or carboxyl group), in the presence of an free-radical initiator. Generally, the molar ratio of chain transfer agent to that of all of vinylic monomers other than the reactive vinylic monomer is from about 1:5 to about 1:100, whereas the molar ratio of chain transfer agent to the reactive vinylic monomer is 1:1. In such preparation, the chain transfer agent with amino or carboxyl group is used to control the molecular weight of the resultant hydrophilic polymer and forms a terminal end of the resultant hydrophilic polymer so as to provide the resultant hydrophilic polymer with one terminal amino or carboxyl group, while the reactive vinylic monomer provides the other terminal carboxyl or amino group to the resultant hydrophilic polymer. Similarly, to prepare a monoamino- or monocarboxyl-terminated homo- or co-polymer of a non-reactive hydrophilic vinylic monomer, the non-reactive vinylic monomer, a chain transfer agent with an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptanes, aminomercaptans, or carboxyl-containing mercaptanes) and optionally other vinylic monomers are copolymerized (thermally or actinically) in the absence of any reactive vinylic monomer.

    [0060] As used herein, a copolymer of a non-reactive hydrophilic vinylic monomer refers to a polymerization product of a non-reactive hydrophilic vinylic monomer with one or more additional vinylic monomers. Copolymers comprising a non-reactive hydrophilic vinylic monomer and a reactive vinylic monomer (e.g., a carboxyl-containing vinylic monomer) can be prepared according to any well-known radical polymerization methods or obtained from commercial suppliers. For example, copolymers containing methacryloyloxyethyl phosphorylcholine and carboxyl-containing vinylic monomer can be obtained from NOP Corporation (e.g., LIPIDURE®-A).

    [0061] The weight average molecular weight Mw of the hydrophilic polymer having at least one amino, carboxyl or thiol group (as a hydrophilicity-enhancing agent) is preferably from about 500 to about 1,000,000, more preferably from about 1,000 to about 500,000, even more preferably from about 5,000 to about 250,000 Daltons.

    [0062] In accordance with the invention, the reaction between a hydrophilicity-enhancing agent and an epichlorohydrin-functionalized polyamine or polyamidoamine is carried out at a temperature of for a period of time sufficient (from about 0.3 hour to about 24 hours, preferably from about 1 hour to about 12 hours, even more preferably from about 2 hours to about 8 hours) to form a water-soluble and thermally-crosslinkable hydrophilic polymeric material containing azetidinium groups.

    [0063] In accordance with the invention, the concentration of a hydrophilicity-enhancing agent relative to an epichlorohydrin-functionalized polyamine or polyamidoamine must be selected not to render a resultant hydrophilic polymeric material water-insoluble (i.e., a solubility of less than 0.005 g per 100 ml of water at room temperature) and not to consume more than about 99%, preferably about 98%, more preferably about 97%, even more preferably about 96% of the azetidinium groups of the epichlorohydrin-functionalized polyamine or polyamidoamine.

    [0064] In accordance with the invention, the step of heating is performed preferably heating the silicone hydrogel contact lens immersed in a packaging solution comprising the hydrophilic polymeric material and at least one buffering agent in an amount sufficient to maintain a pH of from about 6.0 to about 8.5 and has a tonicity of from about 200 to about 450 milliosmol (mOsm) and a viscosity of from about 1 centipoise to about 20 centipoises at 25°C in a lens package to and at a temperature from about 40°C to about 140°C, preferably from about 60°C to about 120°C, even more preferably from about 80°C to about 95°C, for a period of time sufficient to covalently attach the hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through second covalent linkages each formed between one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and/or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens.

    [0065] Lens packages (or containers) are well known to a person skilled in the art for autoclaving and storing a soft contact lens. Any lens packages can be used in the invention. Preferably, a lens package is a blister package which comprises a base and a cover, wherein the cover is detachably sealed to the base, wherein the base includes a cavity for receiving a sterile packaging solution and the contact lens.

    [0066] Lenses are packaged in individual packages, sealed, and sterilized (e.g., by autoclave at about 120°C or higher for at least 30 minutes) prior to dispensing to users. A person skilled in the art will understand well how to seal and sterilize lens packages.

    [0067] In accordance with the invention, a packaging solution contains at least one buffering agent and one or more other ingredients known to a person skilled in the art. Examples of other ingredients include without limitation, tonicity agents, surfactants, antibacterial agents, preservatives, and lubricants (or water-soluble viscosity builders) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone).

    [0068] The packaging solution contains a buffering agent in an amount sufficient to maintain a pH of the packaging solution in the desired range, for example, preferably in a physiologically acceptable range of about 6 to about 8.5. Any known, physiologically compatible buffering agents can be used. Suitable buffering agents as a constituent of the contact lens care composition according to the invention are known to the person skilled in the art. Examples are boric acid, borates, e.g. sodium borate, citric acid, citrates, e.g. potassium citrate, bicarbonates, e.g. sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris (Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane), salts thereof, phosphate buffers, e.g. Na2HPO4, NaH2PO4, and KH2PO4 or mixtures thereof. A preferred bis-aminopolyol is 1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). The amount of each buffer agent in a packaging solution is preferably from 0.001% to 2%, preferably from 0.01 % to 1 %; most preferably from about 0.05% to about 0.30% by weight.

    [0069] The packaging solution has a tonicity of from about 200 to about 450 milliosmol (mOsm), preferably from about 250 to about 350 mOsm. The tonicity of a packaging solution can be adjusted by adding organic or inorganic substances which affect the tonicity. Suitable occularly acceptable tonicity agents include, but are not limited to sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitols, sorbitol, xylitol and mixtures thereof.

    [0070] A packaging solution of the invention has a viscosity of from about 1 centipoise to about 20 centipoises, preferably from about 1.5 centipoises to about 10 centipoises, more preferably from about 2 centipoises to about 5 centipoises, at 25°C.

    [0071] According to the present invention, "in-packaging-coating solution" refers to a package solution comprising a water-soluble and thermally-crosslinkable hydrophilic polymeric material of the invention and/or a polyazetidinium groups-containing component. In a preferred embodiment, the in-packaging-coating solution comprises preferably from about 0.01 % to about 2%, more preferably from about 0.05% to about 1.5%, even more preferably from about 0.1 % to about 1%, most preferably from about 0.2% to about 0.5%, by weight of a water-soluble and thermally-crosslinkable hydrophilic polymeric material of the invention.

    [0072] A silicone hydrogel contact lens obtained according a method of the invention has a surface hydrophilicity/wettability characterized by having an averaged water contact angle of preferably about 90 degrees or less, more preferably about 80 degrees or less, even more preferably about 70 degrees or less, most preferably about 60 degrees or less.

    [0073] In another preferred embodiment, a method of the invention can further comprise, before the step of heating, the steps of: contacting at room temperature the silicone hydrogel contact lens with an aqueous solution of the thermally-crosslinkable hydrophilic polymeric material to form a top layer (i.e., an LbL coating) of the thermally-crosslinkable hydrophilic polymeric material on the surface of the silicone hydrogel contact lens, immersing the silicone hydrogel contact lens with the top layer of the thermally-crosslinkable hydrophilic polymeric material in a packaging solution in a lens package; sealing the lens package; and autoclaving the lens package with the silicone hydrogel contact lens therein to form a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Because of being positively charged, the thermally-crosslinkable hydrophilic polymeric material is believed to be capable of forming, on a silicone hydrogel contact lens, an LbL coating which is not covalently bound to the surface of a silicone hydrogel contact lens (i.e., through physical interactions), especially a contact lens having negatively-charged carboxyl groups on its surface.

    [0074] By "azetidinium groups-containing component" is meant a composition of one or more monomer, oligomer or polymer molecules, or mixtures of one or more thereof, comprising on average at least two (2) azetidinium groups (substituted, unsubstituted or mixtures thereof) per molecule.

    [0075] An azetidinium group is a four membered nitrogen-containing heterocycle, wherein the nitrogen is quarternized, and can be generally depicted by Formula (I):



    [0076] Note that the "double" bonds as depicted in Formula (I) are merely intended to reflect available substituent sites, as further exemplified below.
    Due to the quarternized nitrogen, the azetidinium groups are cationic in nature and this should be taken into account in the formulation of these materials.
    The carbons and nitrogens may be unsubstituted (hydrogen groups) or substituted depending on the particular molecule, albeit one of the nitrogen or opposite carbon (2-carbon) will be linked to or incorporated into a backbone or other bridging group to result in a molecule having at least two azetidinium groups. Molecules containing 2 or more azetidinium groups will be referred to as "polyazetidiniums".

    [0077] In one embodiment, the polyazetidiniums comprise at least two units selected from the group consisting of Formula (II), Formula (III) and mixtures thereof:



    R1 and R2 are independently an alkylene group containing 1 to 6 carbon atoms ("lower alkylene");

    X is an anionic counterion;

    Y1, Y2 and Y3 are each independently selected from the group consisting of hydrogen, hydroxyl, halo, alkoxy, alkyl, amino, carboxy, acetoxy, cyano and sulfhydryl (the groups with carbon atoms preferably having from 1 to 24 carbon atoms); and

    Y4 is a chain-terminating group.



    [0078] Examples of chain-terminating groups include, but are not limited to, hydrogen, alkyl, alkoxy and acyloxy (the groups with carbon atoms preferably having from 1 to 24 carbon atoms).
    Preferred are polymers wherein R1 and R2 are methylene. Preferred counterions, X, include hydrogen sulfate, methane sulfonate, dihydrogen phosphate, nitrate, perchlorate and halide. Y1, Y2 and Y3 are preferably independently hydrogen or lower alkyl (1 to 6 carbon atoms). Y2 is preferably hydrogen or hydroxyl. Particularly preferred substituents are wherein Y1 and Y3 are hydrogen, and/or Y2 is hydroxyl. With regard to the counterions, the ones mentioned are preferred because they have less tendency to react with the azetidinium moiety than the strongly nucleophilic co-reactive species.

    [0079] In one preferred embodiment of a molecule containing groups (II) and/or (III), the polyazetidinium species can be a homopolymer or it can be a copolymer wherein one or more non-azetidinium monomer units are incorporated into backbone structure. The polymer may be essentially straight chain, or it may be branched or crosslinked. Polyazetidiniums can prepared by the reaction of epichlorohydrin with polyamino compounds, oligomers or polymers containing secondary amine groups. Polyamines include polyaminoamides and polyalkylene polyamines.
    Polyaminoamides can be prepared, for example, from diethylene triamine and a dicarboxylic acid such as adipic acid. Reaction of polyaminoamide polymers with epichlorohydrin can form azetidinium groups. The preparation of these sorts of polymers is described in U.S. Pat. No. 6,429,267. A preferred resin is illustrated in Formula (IV)



    [0080] An example of a commercial water-soluble poly(aminoamide)-epichlorohydrin resin is sold under the tradename Kymene™ 557H (Hercules). Polyalkylene polyamines can be made by polymerizing diallylamine. Subsequent reaction with epichlorohydrin can form azetidinium groups, as illustrated in below:



    [0081] Kymene™ ULX wet-strength resin is a polyaminopolyamide-epi resin available from Hercules Incorporated. The one sample has a resin solids of 12.7% and a charge density of 3.36 meq/g at pH 1.8, 1.73 meq/g at pH 8 and 1.51 meq/g at pH 10. The another sample of Kymene™ ULX wet strength resin has a resin solids of 12.7% and a charge density of 3.28 meq/g at pH 1.8, 1.72 meq/g at pH 8 and 1.56 meq/g at pH 10.

    [0082] E7045 wet-strength resin is a polyaminopolyamide-epi resin available from Hercules Incorporated. The sample has a charge density of 3.34 meq/g at pH 1.8, 1.96 meq/g at pH 8 and 0.89 meq/g at pH 10 and a total solids of 13.0%.

    [0083] Kymene™ 557LX wet-strength resin is a polyaminopolyamide-epi resin available from Hercules Incorporated. It has a pH of 3.5, a total solids of 12.5%, and a Brookfield viscosity of 47 cps. It had a charge density of 1.39 meq/g at pH 10.

    [0084] Kymene™ 736 wet-strength resin is a polyalkylene polyamine-epi resin available from Hercules Incorporated. It has a pH of 3.3, a total solids of 37.8%, and a Brookfield viscosity of 250 cps. It has a charge density of 2.24 meq/g at pH 8.

    [0085] Kymene™ ULX2 wet-strength resin is a polyaminopolyamide-epi resin available from Hercules Incorporated.

    [0086] Preparation of these polymers is described in U.S. Pat. Nos. 3,700,623, 3,772,076, 4,298,639 and 4,298,715. Alternatively, the diallylamine can be reacted first with epichlorohydrin and cyclized to the azetidinium monomer, and then polymerized or copolymerized with other unsaturated co-monomers. This approach is described in U.S. Pat. Nos. 4,341,887 and 5,510,004, the disclosures of which are also incorporated by reference herein for all purposes as if fully set forth.

    [0087] According to the present invention, a polyazetidinium groups-containing component is used to reduce the concentration of amino groups and/or carboxyl groups introduced on and/or near the silicone hydrogel contact lens surface during the crosslinked hydrophilic coating process in the first heating step of claim 1 by reaction between azetidinium groups of the polyazetidinium groups-containing component and residual amino groups and/or carboxyl groups remained on and/or the surface of the silicone hydrogel contact lens. The reduction of the concentration of amino groups and/or carboxyl groups introduced on and/or near the silicone hydrogel contact lens surface will reduce its positively charged preservatives or antimicrobial agents such as PHMB uptake during the lens cleaning/disinfecting/storing cycles. The accumulated antimicrobial agents in the lens may subsequence release once the lens is put in to the eye, causing the contact lens wearer's eye irritation. A suitable polyazetidinium groups-containing component can diffuse into the crosslinked hydrophilic coating layer of the silicone hydrogel contact lens and react with residual amino groups and/or carboxyl groups remained on and/or the surface of the silicone hydrogel contact lens to neutralize the residual charge. For example, the polyazetidinium groups-containing component will have molecular weight comparable to or lower than the positively charged preservatives or antimicrobial agents such as PHMB, or Polyquad.

    [0088] Polyquad® (registered trademark of Alcon Laboratories, Inc.) which is also known as Onamer® (registered trademark of Millmaster Onyx Group) has been used successfully to provide disinfecting and preservation properties to contact lens treating solutions, eye drop solutions and preserved saline solutions. The chemical name for Polyquad® is alpha-4-[1-tris(2-hydroxyethyl)ammonium-2-butenyl]poly[1-dimethylammon ium-2-butenyl]-.omega.-tris(2 hydroxyethyl)ammonium chloride. The salt has an average molecular weight generally in the range of from about 2,000 to about 30,000 and preferably in the range of about 3,000 to about 14,000. Ophthalmic compositions containing Polyquad® and methods for disinfecting contact lenses with solutions containing this polymer are disclosed in U.S. Pat. Nos. 5,037,647; 4,525,346 and 4,407,791.

    [0089] PHMB, a poly(hexamethylene) biguanide, is described for use as antimicrobial agents in contact lens solution in U.S. Pat. No. 4,758,595. The patent discloses that molecular weight of PHMB can be up to approximately 100, 1000 and preferably from 1,000 to 50,000.

    [0090] According to the present invention, a polyamidoamine epichlorohydrin with a wide range of molecular weight, as indicted by solution viscosity (at 23% solid) range of from 10 to 200 m.Pa.s, preferably from 30 to 160 m.Pa.s. and more preferably from 40 to 130 m.Pa.s .

    [0091] The polyazetidinium groups-containing component is present in the packaging solution in an amount of from about 0.01% to about 5% by weight, preferably from about 0.05% to about 3% by weight, even more preferably from about 0.1 % to about 1 % by weight, based on the total amount of the packaging solution.

    [0092] In accordance with the invention, the step of reducing the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens is performed preferably by autoclaving the silicone hydrogel contact lens immersed in a packaging solution (i.e., a buffered aqueous solution) in a sealed lens package at a temperature of from about 118 °C to about 125°C for approximately 20-90 minutes. In accordance with this embodiment of the invention, the packaging solution is a buffered aqueous solution which is ophthalmically safe after autoclave.

    [0093] It should be understood that although various embodiments including preferred embodiments of the invention may be separately described above, they can be combined and/or used together in any desirable fashion in the method of the invention for producing silicone hydrogel contact lenses each having a crosslinked hydrophilic coating thereon.

    [0094] Various embodiments including preferred embodiments of silicone hydrogel contact lenses inherently having amino groups and/or carboxyl groups, silicone hydrogel contact lenses having a reactive base coating, reactive vinylic monomers, non-reactive vinylic monomers, reactive polymers for forming a reactive LbL base coating, plasma coatings, epichlorohydrin-functionalized polyamine or polyamidoamine, hydrophilicity enhancing agents, water-soluble hydrophilic polymeric materials with azetidinium groups, the step of heating, lens packages, packaging solutions, and surface wettability of a siiicone hydrogel contact lens with a crosslinked hydrophilic coating of the invention are described above and can be combined and/or used together in these two aspects of the invention.

    [0095] The previous disclosure will enable one having ordinary skill in the art to practice the invention. Various modifications, variations, and combinations can be made to the various embodiment described herein. In order to better enable the reader to understand specific embodiments and the advantages thereof, reference to the following examples is suggested. It is intended that the specification and examples be considered as exemplary.

    [0096] PHMB (Polyhexamethylene Biguanide) Uptake Measurement.
    Each lens is soaked overnight in 3ml of 10ppm of PHMB. The uptake of PHMB into the lens is measured by the depletion of PHMB from the absorption of a UV peak at 240nm.

    Lubricity Evaluation



    [0097] The lubricity rating is a qualitative ranking scheme where a scale of 0 to 4 is used with 0 or lower numbers indicating better lubricity, 1 is assigned to Oasys™/TruEye™ commercial lenses and 4 is assigned to commercial Air Optix™ lenses. The samples are rinsed with excess DI water for at least three times and then transferred to PBS before the evaluation. Before the evaluation, hands are rinsed with a soap solution, extensively rinsed with DI water and then dried with KimWipe® towels. The samples are handled between the fingers and a numerical number is assigned for each sample relative to the above standard lenses described above. For example, if lenses are determined to be only slightly better than Air Optix™ lenses, then they are assigned a number 3. For consistency, all ratings are independently collected by the same two operators in order to avoid bias and the data so far reveal very good qualitative agreement and consistency in the evaluation.
    Surface hydrophilicity/wetability Tests. Water contact angle on a contact lens is a general measure of the surface hydrophilicity (or wetability) of the contact lens. In particular, a low water contact angle corresponds to more hydrophilic surface. Average contact angles (Sessile Drop) of contact lenses are measured using a VCA 2500 XE contact angle measurement device from AST, Inc., located in Boston, Massachusetts. This equipment is capable of measuring advancing or receding contact angles or sessile (static) contact angles. The measurements are performed on fully hydrated contact lenses and immediately after blot-drying as follows. A contact lens is removed from the vial and washed 3 times in ∼200ml of fresh DI water in order to remove loosely bound packaging additives from the lens surface. The lens is then placed on top of a lint-free clean cloth (Alpha Wipe TX1009), dabbed well to remove surface water, mounted on the contact angle measurement pedestal, blown dry with a blast of dry air and finally the sessile drop contact angle is automatically measured using the software provided by the manufacturer. The DI water used for measuring the contact angle has a resistivity > 18MΩcm and the droplet volume used is 2µl. Typically, uncoated silicone hydrogel lenses (after autoclave) have a sessile drop contact angle around 120 degrees. The tweezers and the pedestal are washed well with Isopropanol and rinsed with DI water before coming in contact with the contact lenses.
    Water Break-up Time (WBUT) Tests. The wettabilty of the lenses (after autoclave) is also assessed by determining the time required for the water film to start breaking on the lens surface. Briefly, lenses are removed from the vial and washed 3 times in ∼ 200ml of fresh DI water in order to remove loosely bound packaging additives from the lens surface. The lens is removed from the solution and held against a bright light source. The time that is needed for the water film to break (de-wet) exposing the underlying lens material is noted visually. Uncoated lenses typically instantly break upon removal from DI water and are assigned a WBUT of 0 seconds. Lenses exhibiting WBUT ≥ 5 seconds are considered wettable and are expected to exhibit adequate wettability (ability to support the tear film) on-eye.

    Example 1


    Preparation of Chain-Extended Polydimethylsiloxane Vinylic Macromer with Terminal Methacrylate Groups (CE-PDMS Macromer)



    [0098] In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn = 2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate (IPDI) by reacting 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g IPDI in 150 g of dry methyl ethyl ketone (MEK) in the presence of 0.063g of dibutyltindilaurate (DBTDL). The reaction is kept for 4.5 h at 40° C, forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn = 3000, Shin-Etsu, KF-6002) and 50 g of dry MEK are added dropwise to the IPDI-PDMS-IPDI solution to which has been added an additional 0.063 g of DBTDL. The reactor is held for 4.5 h at about 40° C, forming HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK is then removed under reduced pressure. In the third step, the terminal hydroxyl-groups are capped with methacryloyloxyethyl groups in a third step by addition of 7.77 g of isocyanatoethylmethacrylate (IEM) and an additional 0.063 g of DBTDL, forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM.

    Alternate Preparation of CE-PDMS Macromer with Terminal Methacrylate Groups



    [0099] 240.43 g of KF-6001 is added into a 1-L reactor equipped with stirring, thermometer, cryostat, dropping funnel, and nitrogen/vacuum inlet adapter, and then dried by application of high vacuum (2×10-2 mBar). Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK is then added into the reactor and the mixture is stirred thoroughly. 0.235 g of DBTDL is added to the reactor. After the reactor is warmed to 45°C, 45.86 g of IPDI are added through an addition funnel over 10 minutes to the reactor under moderate stirring. The reaction is kept for 2 hours at 60°C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are then added and stirred until a homogeneous solution is formed. 0.235 g of DBTDL are added, and the reactor is held at about 55°C overnight under a blanket of dry nitrogen. The next day, MEK is removed by flash distillation. The reactor is cooled and 22.7 g of IEM are then charged to the reactor followed by about 0.235 g of DBTDL. After about 3 hours, an additional 3.3 g of IEM are added and the reaction is allowed to proceed overnight. The following day, the reaction mixture is cooled to about 18°C to obtain CE-PDMS macromer with terminal methacrylate groups.

    Preparation of Lens Formulations



    [0100] A lens formulation is prepared by dissolving components in 1-propanol to have the following composition: 33% by weight of CE-PDMS macromer prepared in Example 2, 17% by weight of N-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% by weight of N,N-dimethylacrylamide (DMA), 0.5% by weight of N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt) (L-PEG), 1.0% by weight Darocur 1173 (DC1173), 0.1% by weight of visitint (5% copper phthalocyanine blue pigment dispersion in tris(trimethylsiloxy)silylpropylmethacrylate, TRIS), and 24.5% by weight of 1-propanol.

    Preparation of Lenses



    [0101] Lenses are prepared by cast-molding from the lens formulation prepared above in a reusable mold, similar to the mold shown in Figs. 1-6 in U.S. patent Nos.7,384,590 and 7,387,759 (Figs. 1-6). The mold comprises a female mold half made of quartz (or CaF2) and a male mold half made of glass (or PMMA). The UV irradiation source is a Hamamatsu lamp with the WG335 +TM297 cut off filter at an intensity of about 4 mW /cm2. The lens formulation in the mold is irradiated with UV irradition for about 25 seconds. Cast-molded lenses are extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed in water, coated with polyacrylic acid (PAA) by dipping lenses in a propanol solution of PAA (0.1 % by weight, acidified with formic acid to about pH 2.5), and hydrated in water. Resultant lenses having a reactive PAA-LbL base coating thereon are determined to have the following properties: ion permeability of about 8.0 to about 9.0 relative to Alsacon lens material; apparent Dk (single point) of about 90 to 100; a water content of about 30% to about 33%; and an elastic modulus of about 0.60 MPa to about 0.65 MPa.

    Example 2


    Charge neutralization of IPC #1 with PAE with relatively high viscosity



    [0102] Lenses with PAA-x-PAE-x-PAAm/PAA in packaging coating (referred to as IPC #1 in this application) were prepared using the procedures shown in US2012/0026457 A1.

    [0103] Poly(acrylamide-co-acrylic acid) partial sodium salt (∼90% solid content, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased from Polysciences, Inc. and used as received.

    [0104] An IPC saline is prepared by dissolving 0.07% of PAAm-PAA (90/10) and 0.2% of PAE (Kymene) in PBS and adjusting the pH to 7.2-7.4. Then the saline is heat pre-treated for about 4 hours at about 70°C or 6hr at about 60 °C, forming a water-soluble and thermally-crosslinkable hydrophilic polymeric material containing azetidinium groups. After the heat pre-treatment, the IPC saline is filtered using a 0.22micron polyether sulphone [PES] membrane filter and cooled down back to room temperature.

    [0105] Lenses having a PAA- base coating are placed in a polypropylene lens packaging shells with 0.6 mL of the heat-pretreated IPC saline (half of the IPC saline is added prior to inserting the lens). The blister is then sealed with foil and autoclaved for about 30 minutes at 121°C, forming a crosslinked coating (PAA-x-PAEXPAAm-PAA) on the lenses. A charge-neutralization saline #1 (CNS #1) is prepared by dissolving appropriate concentration of PAE in PBS (phosphate buffered saline). For example, 1% of PAE (from Kymene VSP33PL liquid, with a viscosity of 126 m.Pa.s at 25% solid) in PBS was prepared by simply adding 1g of PAE to 100ml of PBS. The packaging shells of above-mentioned lenses with IPC #1 coating were opened. Then the lenses are repackaged in either PBS or CNS#1 and autoclaved for 45 min.

    [0106] The lenses are tested for PHMB uptake. Each lens is soaked overnight in 3ml of 10ppm of PHMB. The uptake of PHMB into the lens is measured by the depletion of PHMB from the absorption of a UV peak at 240nm.

    [0107] The PHMB uptake for the test lenses (autoclaved in CNS#1) is 14.2±1.9 micrograms per lens, which is lower than 17.8 ±1.2 micrograms per lens for control lenses (autoclaved in PBS). This represent 20.2% reduction in PHMB uptake for the test lenses treated with 1 % relatively high viscosity PAE in a phosphate buffered saline compare to the control lens.

    Example 3


    Charge neutralization of IPC #1 with PAE with relatively low viscosity (as compared to PAE from example 2)



    [0108] Lenses with PAA-x-PAE-x-PAAm/PAA in packaging coating (referred to as IPC #1 in this application) were prepared using the procedures shown in US2012/0026457 A1 and as described above in example #2. A charge-neutralization saline #2 (CNS #2) is prepared by dissolving appropriate concentration of PAE in PBS (phosphate buffered saline). For example, 0.5% of PAE (from Amres MOC-3029 liquid, with a viscosity of 44 m.Pa.s at 20% solid) in PBS was prepared by simply adding 0.5g of PAE to 100ml of PBS. The packaging shells of above-mentioned lenses with IPC #1 coating were opened. Then the lenses are repackaged in either PBS or CNS#1 and autoclaved for 45 min.

    [0109] The lenses are tested for PHMB uptake. Each lens is soaked overnight in 3ml of 10ppm of PHMB. The uptake of PHMB into the lens is measured by the depletion of PHMB from the absorption of a UV peak at 240nm.

    [0110] The PHMB uptake for the test lenses (autoclaved in CNS#2) is 12.2±0.8 micrograms per lens, which is lower than 20.4 ±1.2 micrograms per lens for control lenses (autoclaved in PBS). This represent 40.2% reduction in PHMB uptake for the test lenses treated with 0.5% relatively low viscosity PAE in a phosphate buffered saline compare to the control lens.

    [0111] The finger lubricity is rated as 4 for the test lenses, in a 0 to 4 scale (0 is most lubricious and 4 is the least lubricious). The finger lubricity is rated as 0 for the control lenses. The water contact angle is 36 for the test lenses and 38 for the control lenses. The WBUT(water beak up time) is about 6 seconds for the test lenses and about 15 seconds for the control lenses.

    Example 4


    Charge neutralization of IPC #1 with PAE with relatively low viscosity (as compared to PAE from example 2)



    [0112] Lenses with PMAA-x-PAE-x-PAAm-PAA in packaging coating (referred to as IPC #1 in this application) were prepared using the procedures shown in US2012/0026457 A1 and as described above in example #2.. A charge-neutralization saline #3 (CNS #3) is prepared by dissolving appropriate concentration of PAE in PBS (phosphate buffered saline). For example, 1 % of PAE (from Amres MOC-3029 liquid, with a viscosity of 44 m.Pa.s at 20% solid) in PBS was prepared by simply adding 1g of PAE to 100ml of PBS. The packaging shells of above-mentioned lenses with IPC #1 coating were opened. Then the lenses are repackaged in either PBS or CNS#1 and autoclaved for 45 min.

    [0113] The lenses are tested for PHMB uptake. Each lens is soaked overnight in 3ml of 10ppm of PHMB. The uptake of PHMB into the lens is measured by the depletion of PHMB from the absorption of a UV peak at 240nm.

    [0114] The PHMB uptake for the test lenses (autoclaved in CNS#3) is 14.3±0.5 micrograms per lens, which is lower than 20.4 ±1.2 micrograms per lens for control lenses (autoclaved in PBS). This represent 30% reduction in PHMB uptake for the test lenses treated with 1% relatively low viscosity PAE in a phosphate buffered saline compare to the control lens.

    [0115] The finger lubricity is rated as 4 for the test lenses, in a 0 to 4 scale (0 is most lubricious and 4 is the least lubricious). The finger lubricity is rated as 0 for the control lenses. The water contact angle is 39 for the test lenses and 38 for the control lenses. The WBUT(water beak up time) is about 6 seconds for the test lenses and about 15 seconds for the control lenses.

    Example #5: Charge neutralization of IPC #2 with PAE with relatively low viscosity (as compared to PAE from example 2)



    [0116] Lenses with PMAA-x-PAE-x-PEG in packaging coating (referred to as IPC #2 in this application) were prepared using the procedures shown in US2012/0026457 A1.. A reaction mixture is prepared by dissolving 2.86% by weight of methoxy-poly (ethyleneglycol)-thiol, avg Mw 2000 (Product #MPEG-SH-2000, Laysan Bio Inc.) along with 2% by weight of PAE (Kymene) in PBS and the final pH adjusted to 7.5. The solution is heat-treated under nitrogen for about 4 hours at 45 °C forming a thermally crosslinkable hydrophilic polymeric material containing MPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the Azetidinium groups in PAE. After the heat-treatment, the solution is diluted 10-fold with PBS containing 0.25% sodium citrate, pH adjusted to 7.2-7.4, and then filtered using 0.22micron polyether sulphone (PES) membrane filter. The final IPC saline contains 0.286% by weight of hydrophilic polymeric material (consisting of about 59% by weight of MPEG-SH-2000 chains and about 41% by weight of PAE chains) and 0.25% Sodium citrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2PO4.H2O and 0.353% Na2HPO4.2H2O in water.

    [0117] There are two differences between IPC #1 and IPC #2: (1) PAA (poly(acrylic acid)) in IPC #1 is replaced with PMAA (poly(methylacrylic acid)); (2) PAAm-PAA in IPC #1 is replaced by PEG (polyethylene glycol).
    A charge-neutralization saline #3 (CNS #3) is prepared by dissolving appropriate concentration of PAE in PBS (phosphate buffered saline). For example, 1% of PAE (from Amres MOC-3029 liquid, with a viscosity of 44 m.Pa.s at 20% solid) in PBS was prepared by simply adding 1g of PAE to 100ml of PBS. The packaging shells of above-mentioned lenses with IPC #1 coating were opened. Then the lenses are repackaged in either PBS or CNS#1 and autoclaved for 45 min.

    [0118] The lenses are tested for PHMB uptake. Each lens is soaked overnight in 3ml of 10ppm of PHMB. The uptake of PHMB into the lens is measured by the depletion of PHMB from the absorption of a UV peak at 240nm.

    [0119] The PHMB uptake for the test lenses (autoclaved in CNS#3) is 0.4±0.2 micrograms per lens, which is lower than 1.4 ±0.3 micrograms per lens for control lenses (autoclaved in PBS). This represent 71.4% reduction in PHMB uptake for the test lenses treated with 1 % relatively low viscosity PAE in a phosphate buffered saline compare to the control lens.

    [0120] The finger lubricity is rated as 1 for the test lenses, in a 0 to 4 scale (0 is most lubricious and 4 is the least lubricious). The finger lubricity is rated as 0.5 for the control lenses. The water contact angle is 41 for the test lenses and 41 for the control lenses. The WBUT(water beak up time) is about 6 seconds for the test lenses and about 5 seconds for the control lenses


    Claims

    1. A method for producing silicone hydrogel contact lenses with crosslinked hydrophilic coatings thereon, comprising the steps of:

    (a) obtaining a silicone hydrogel contact lens having amino groups and/or carboxyl groups on and/or near its surface and a water-soluble and thermally-crosslinkable hydrophilic polymeric material, wherein the silicone hydrogel contact lens comprises amino groups or carboxyl groups or both on and/or near the surface of the contact lens, wherein the hydrophilic polymeric material comprises (i) from about 20% to about 95 by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof, and (iii) positively-charged azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains through one or more covalent linkages each formed between one azetitdinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and

    (b) heating the silicone hydrogel contact lens immersed in a packaging solution comprising the hydrophilic polymeric material and at least one buffering agent in an amount sufficient to maintain a pH of from about 6.0 to about 8.5 and has a tonicity of from about 200 to about 450 milliosmol (mOsm) and a viscosity of from about 1 centipoise to about 20 centipoises at 25°C in a lens package to and at a temperature from about 40°C to about 140°C for a period of time sufficient to covalently attach the hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through second covalent linkages each formed between one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and/or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens,

    (c) adding a polyazetidinium groups-containing component into the package solution with the silicone contact lens of the step (b), wherein the polyazetidinium groups-containing component comprise at least two groups selected from the group consisting of Formula (II), Formula (III) and mixtures thereof:



    wherein: R1 and R2 are independently an alkylene group containing 1 to 6 carbon atoms; X is an anionic counterion; Y1, Y2 and Y3 are each independently selected from the group consisting of hydrogen, hydroxyl, halo, alkoxy, alkyl, amino, carboxy, acetoxy, cyano and sulfhydryl; and Y4 is a chain-terminating group, selected from the group consisting of hydrogen, alkyl, alkoxy and acyloxy;

    (d) sealing the lens package with the contact lens and the package solution of step (c)

    (e) reducing the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens by autoclaving the package with the contact lens and the in-package-coating solution therein of step (d) and inducing reaction between azetidinium groups of the polyazetidinium groups-containing component and residual amino groups and/or carboxyl groups remained on and/or the surface of the silicone hydrogel contact lens immersed in the in-package-coating solution, wherein the reduction of the concentration of carboxyl groups on and/or near the silicone hydrogel contact lens of step (e) is characterized by having an decreased positively charged preservatives uptake in relation to the silicone hydrogel contact lens of step (b) by at least 20%.


     
    2. The method of claim 1, wherein the polyazetidinium groups-containing component has a solution viscosity range of 10 to 200 m.Pa.s at 23% solid.
     
    3. The method of claim 2, wherein the polyazetidinium groups-containing component has a solution a viscosity range of 30 to 160 m.Pa.s at 23% solid.
     
    4. The method of claim 3, wherein the polyazetidinium groups-containing component has a solution a viscosity range of 40 to 130 m.Pa.s at 23% solid.
     
    5. The method of any one of claims 1 to 4, wherein the in-packaging-coating solution of step (b) comprises from 0.01 % to 2% by weight of thermally-crosslinkable hydrophilic polymeric material.
     
    6. The method of any one of claims 1 to 5, wherein the polyazetidinium groups-containing component is added in the in-packaging-coating solution of step (c) in an amount of from about 0.01 % to about 5% by weight based on the total amount of the in - packaging-coating solution.
     
    7. The method of any one of claims 1 to 6, wherein the step of heating is perform by heating the silicone hydrogel contact lens immersed in a packaging solution in a sealed lens package at a temperature from about 40°C to about 140°C for approximately 20-180 minutes and the step of reducing the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens by autoclaving the package with the contact lens and the in-package-coating solution at a temperature of from about 118°C to about 125°C for approximately 20-90 minutes.
     
    8. The method of claim 7, wherein the step of heating is perform by heating the silicone hydrogel contact lens immersed in a packaging solution in a sealed lens package at a temperature from about 75°C to about 95°C for approximately 20-180 minutes and the step of reducing the concentration of amino groups and/or carboxyl groups on and/or near the silicone hydrogel contact lens by autoclaving the package with the contact lens and the in-package-coating solution at a temperature of from about 118°C to about 125°C for approximately about 118°C to about 125°C for approximately 20-40 minutes.
     
    9. The method of any one of claims 1 to 8, wherein the hydrophilicity-enhancing agent is a hydrophilic polymers having one or more amino, carboxyl and/or thiol groups, wherein the content of monomeric units having an amino, carboxyl or thiol group in the hydrophilic polymer as the hydrophilicity-enhancing agent is less than about 40% by weight based on the total weight of the hydrophilic polymer.
     
    10. The method of any one of claims 1 to 9, wherein the weight average molecular weight Mw of the hydrophilic polymer having at least one amino, carboxyl or thiol group from about 500 to about 1,000,000 Daltons.
     
    11. The method of any one of claims 1 to 10, wherein the silicone hydrogel contact lens comprises a reactive base coating including amino and/or carboxyl groups.
     
    12. The method of claim 11, wherein the reactive base coating comprises at least one layer of a reactive polymer having pendant amino groups and/or carboxyl groups and is obtained by contacting the silicone hydrogel contact lens with a solution of the reactive polymer, wherein the reactive polymer is: a homopolymer of amino-C1 to C4 alkyl (meth)acrylamide, amino-C1 to C4 alkyl (meth)acrylate, C1 to C4 alkylamino-C1 to C4 alkyl (meth)acrylamide, C1 to C4 alkylamino-C1 to C4 alkyl (meth)acrylate, allylamine, or vinylamine; polyethyleneimine; a polyvinylalcohol with pendant amino groups; a linear or branched polyacrylic acid; a homopolymer of C1 to C12 alkylacrylic acid; a copolymer of amino-C2 to C4 alkyl (meth)acrylamide, amino-C2 to C4 alkyl (meth)acrylate, C1 to C4 alkylamino-C2 to C4 alkyl (meth)acrylamide, C1 to C4 alkylamino-C2 to C4 alkyl (meth)acrylate, acrylic acid, C1 to C12 alkylacrylic acid, maleic acid, and/or fumaric acid, with at least one non-reactive hydrophilic vinylic monomer; a carboxyl-containing cellulose; hyaluronate; chondroitin sulfate; poly(glutamic acid); poly(aspartic acid); or combinations thereof.
     
    13. The method of claim 12, wherein the reactive polymer for forming a base coating is polyacrylic acid, polymethacrylic acid, poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinylacetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylamine homo- or copolymer, or combinations thereof.
     
    14. The method of claim 12 or 13, wherein the weight average molecular weight Mw of a reactive polymer for forming a reactive base coating is at least about 10,000 Daltons.
     
    15. The method of claim 14, wherein the weight average molecular weight Mw of a reactive polymer for forming a reactive base coating is from about 10,000 to 1,000,000 Daltons.
     
    16. The method of any one of claims 12 to 15, wherein the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents.
     


    Ansprüche

    1. Verfahren zur Herstellung von Silikonhydrogel-Kontaktlinsen mit vernetzten hydrophilen Beschichtungen darauf, umfassend die Schritte:

    (a) Erhalten einer Silikonhydrogel-Kontaktlinse mit Aminogruppen und/oder Carboxylgruppen auf und/oder in der Nähe ihrer Oberfläche und einem wasserlöslichen und thermisch vernetzbaren hydrophilen Polymermaterial, wobei die Silikonhydrogel-Kontaktlinse Aminogruppen oder Carboxylgruppen oder beide an und/oder in der Nähe der Oberfläche der Kontaktlinse umfasst, wobei das hydrophile Polymermaterial umfasst (i) etwa 20 Gew.-% bis etwa 95 Gew.-% erste Polymerketten, die von einem Epichlorhydrin-funktionalisierten Polyamin oder Polyamidoamin abgeleitet sind, (ii) etwa 5 Gew.-% bis etwa 80 Gew.-% hydrophile Einheiten oder zweite Polymerketten, die von mindestens einem hydrophiliesteigernden Mittel mit mindestens einer reaktiven funktionellen Gruppe, ausgewählt aus der Gruppe bestehend aus Aminogruppe, Carboxylgruppe, Thiolgruppe und Kombination davon, abgeleitet sind, und (iii) positiv geladene Azetidiniumgruppen, die Teile der ersten Polymerketten oder seitenständige oder endständige Gruppen sind, die kovalent an die ersten Polymerketten gebunden sind, wobei die hydrophilen Einheiten oder zweiten Polymerketten durch eine oder mehrere kovalente Bindungen, die jeweils zwischen einer Azetitdiniumgruppe des Epichlorhydrin-funktionalisierten Polyamins oder Polyamidoamins und einer Amino-, Carboxyl- oder Thiolgruppe des hydrophiliesteigernden Mittels gebildet sind, kovalent an die ersten Polymerketten gebunden sind; und

    (b) Erwärmen der Silikonhydrogel-Kontaktlinse, die in eine Verpackungslösung getaucht ist, die das hydrophile Polymermaterial und mindestens ein Puffermittel in einer ausreichenden Menge enthält, so dass ein pH-Wert von etwa 6,0 bis etwa 8,5 aufrechterhalten wird, und die eine Tonizität von etwa 200 bis etwa 450 Milliosmol (mOsm) und eine Viskosität von etwa 1 Centipoise bis etwa 20 Centipoise bei 25°C aufweist, in einer Linsenverpackung auf und bei einer Temperatur von etwa 40°C bis etwa 140°C für einen ausreichenden Zeitraum, um das hydrophile Polymermaterial kovalent an die Oberfläche der Silikonhydrogel-Kontaktlinse durch zweite kovalente Bindungen, die jeweils zwischen einer Azetidiniumgruppe des hydrophilen Polymermaterials und einer der reaktiven funktionellen Gruppen an und/oder in der Nähe der Oberfläche der Kontaktlinse gebildet sind, zu binden, wodurch eine vernetzte hydrophile Beschichtung auf der Silikonhydrogel-Kontaktlinse gebildet wird,

    (c) Zugeben einer Polyazetidiniumgruppen enthaltenden Komponente in die Verpackungslösung mit der Silikon-Kontaktlinse von Schritt (b), wobei die Polyazetidiniumgruppen enthaltende Komponente mindestens zwei Gruppen umfasst, die ausgewählt sind aus der Gruppe, bestehend aus Formel (II), Formel (III) und Gemischen davon:



    worin: R1 und R2 unabhängig voneinander eine 1 bis 6 Kohlenstoffatome enthaltende Alkylengruppe sind; X ein anionisches Gegenion ist; Y1, Y2 und Y3 jeweils unabhängig ausgewählt sind aus der Gruppe bestehend aus Wasserstoff, Hydroxyl, Halogen, Alkoxy, Alkyl, Amino, Carboxy, Acetoxy, Cyano und Sulfhydryl; und Y4 eine Kettenabbruchgruppe ist, ausgewählt aus der Gruppe bestehend aus Wasserstoff, Alkyl, Alkoxy und Acyloxy;

    (d) Versiegeln der Linsenverpackung mit der Kontaktlinse und der Verpackungslösung aus Schritt (c);

    (e) Reduzieren der Konzentration von Aminogruppen und/oder Carboxylgruppen an und/oder in der Nähe der Silikonhydrogel-Kontaktlinse durch Autoklavieren der Verpackung mit der Kontaktlinse und der in der Verpackung befindlichen Beschichtungslösung von Schritt (d) und Induzieren einer Reaktion zwischen Azetidiniumgruppen der Polyazetidiniumgruppen enthaltenden Komponente und den restlichen Aminogruppen und/oder Carboxylgruppen, die auf und/oder der Oberfläche der Silikonhydrogel-Kontaktlinse verbleiben, die in der in der Verpackung befindlichen Beschichtungslösung eingetaucht ist, wobei die Verringerung der Konzentration von Carboxylgruppen an und/oder in der Nähe der Silikonhydrogel-Kontaktlinse von Schritt (e) dadurch gekennzeichnet ist, dass sie eine verminderte Aufnahme positiv geladener Konservierungsmittel in Bezug auf die Silikonhydrogel-Kontaktlinse von Schritt (b) um mindestens 20% aufweist.


     
    2. Verfahren nach Anspruch 1, wobei die Polyazetidiniumgruppen enthaltende Komponente einen Lösungsviskositätsbereich von 10 bis 200 m · Pa · s bei 23% Feststoff aufweist.
     
    3. Verfahren nach Anspruch 2, wobei die Polyazetidiniumgruppen enthaltende Komponente einen Lösungsviskositätsbereich von 30 bis 160 m · Pa · s bei 23% Feststoff aufweist.
     
    4. Verfahren nach Anspruch 3, wobei die Polyazetidiniumgruppen enthaltende Komponente einen Lösungsviskositätsbereich von 40 bis 130 m · Pa · s bei 23% Feststoff aufweist.
     
    5. Verfahren nach einem der Ansprüche 1 bis 4, wobei die in der Verpackung befindliche Beschichtungslösung von Schritt (b) 0,01 Gew.-% bis 2 Gew.-% thermisch vernetzbares hydrophiles Polymermaterial umfasst.
     
    6. Verfahren nach einem der Ansprüche 1 bis 5, wobei die Polyazetidiniumgruppen enthaltende Komponente in der in der Verpackung befindlichen Beschichtungslösung von Schritt (c) in einer Menge von etwa 0,01 Gew.-% bis etwa 5 Gew.-%, bezogen auf die Gesamtmenge der in der Verpackung befindlichen Beschichtungslösung, zugegeben wird.
     
    7. Verfahren nach einem der Ansprüche 1 bis 6, wobei der Erwärmungsschritt durch Erwärmen der in einer Verpackungslösung eingetauchten Silikonhydrogel-Kontaktlinse in einer versiegelten Linsenverpackung bei einer Temperatur von etwa 40°C bis etwa 140°C für etwa 20 bis 180 Minuten, und der Schritt des Reduzierens der Konzentration an Aminogruppen und/oder Carboxylgruppen an und/oder in der Nähe der Silikonhydrogel-Kontaktlinse durch Autoklavieren der Verpackung mit der Kontaktlinse und der in der Verpackung befindlichen Beschichtungslösung bei einer Temperatur von etwa 118°C bis etwa 125°C für etwa 20 bis 90 Minuten erfolgt.
     
    8. Verfahren nach Anspruch 7, wobei der Erwärmungsschritt durch Erwärmen der in einer Verpackungslösung eingetauchten Silikonhydrogel-Kontaktlinse in einer versiegelten Linsenverpackung bei einer Temperatur von etwa 75°C bis etwa 95°C für etwa 20 bis 180 Minuten und der Schritt des Reduzierens der Konzentration an Aminogruppen und/oder Carboxylgruppen an und/oder in der Nähe der Silikonhydrogel-Kontaktlinse durch Autoklavieren der Verpackung mit der Kontaktlinse und der in der Verpackung befindlichen Beschichtungslösung bei einer Temperatur von etwa 118°C bis etwa 125°C für etwa 118°C bis etwa 125°C für etwa 20 bis 40 Minuten erfolgt.
     
    9. Verfahren nach einem der Ansprüche 1 bis 8, wobei das hydrophiliesteigernde Mittel ein hydrophiles Polymer mit einer oder mehreren Amino-, Carboxyl- und/oder Thiolgruppen ist, wobei der Gehalt an Monomereinheiten mit einer Amino-, Carboxyl- oder Thiolgruppe im hydrophilen Polymer als hydrophiliesteigerndes Mittel weniger als etwa 40 Gew.-%, bezogen auf das Gesamtgewicht des hydrophilen Polymers, beträgt.
     
    10. Verfahren nach einem der Ansprüche 1 bis 9, wobei das Gewichtsmittel des Molekulargewichts Mw des hydrophilen Polymers mit mindestens einer Amino-, Carboxyl- oder Thiolgruppe von etwa 500 bis etwa 1000000 Dalton reicht.
     
    11. Verfahren nach einem der Ansprüche 1 bis 10, wobei die Silikonhydrogel-Kontaktlinse eine reaktive Basisbeschichtung umfasst, die Amino- und/oder Carboxylgruppen umfasst.
     
    12. Verfahren nach Anspruch 11, wobei die reaktive Basisbeschichtung mindestens eine Schicht eines reaktiven Polymers mit seitenständigen Aminogruppen und/oder Carboxylgruppen umfasst und durch Zusammenbringen der Silikonhydrogel-Kontaktlinse mit einer Lösung des reaktiven Polymers erhalten wird, wobei das reaktive Polymer ist: ein Homopolymer von Amino-C1- bis C4-alkyl (meth) acrylamid, Amino-C1- bis C4-alkyl(meth)acrylat, C1- bis C4-Alkylamino-C1- bis C4-alkyl(meth)acrylamid, C1- bis C4-Alkylamino-C1- bis C4-alkyl(meth)acrylat, Allylamin oder Vinylamin; Polyethylenimin; ein Polyvinylalkohol mit seitenständigen Aminogruppen; eine lineare oder verzweigte Polyacrylsäure; ein Homopolymer von C1- bis C12-Alkylacrylsäure; ein Copolymer von Amino-C2- bis C4-alkyl(meth)acrylamid, Amino-C2- bis C4-alkyl(meth)acrylat, C1- bis C4-Alkylamino-C2- bis C4-alykl(meth)acrylamid, C1- bis C4-Alkylamino-C2- bis C4-alkyl(meth)acrylat, Acrylsäure, C1- bis C12-Alkylacrylsäure, Maleinsäure und/oder Fumarsäure, mit mindestens einem nicht reaktiven hydrophilen Vinylmonomer; eine Carboxyl-enthaltende Cellulose; Hyaluronat; Chondroitinsulfat; Poly(glutaminsäure); Poly(asparaginsäure); oder Kombinationen davon.
     
    13. Verfahren nach Anspruch 12, wobei das reaktive Polymer zur Bildung einer Basisbeschichtung Polyacrylsäure, Polymethacrylsäure, Poly(N,N-2-acrylamidoglykolsäure), Poly[(meth)acrylsäure-co-acrylamid], Poly[(meth)acrylsäure-co-vinylpyrrolidon], hydrolysiertes Poly[(meth)acrylsäure-co-vinylacetat], Polyethylenimin (PEI), Polyallylaminhydrochlorid (PAH) Homo- oder Copolymer, Polyvinylaminhomo- oder - copolymer oder Kombinationen davon ist.
     
    14. Verfahren nach Anspruch 12 oder 13, wobei das Gewichtsmittel des Molekulargewichts Mw eines reaktiven Polymers zur Bildung einer reaktiven Basisbeschichtung mindestens etwa 10000 Dalton beträgt.
     
    15. Verfahren nach Anspruch 14, wobei das Gewichtsmittel des Molekulargewichts Mw eines reaktiven Polymers zur Bildung einer reaktiven Basisbeschichtung etwa 10000 bis 1000000 Dalton beträgt.
     
    16. Verfahren nach einem der Ansprüche 12 bis 15, wobei das reaktive Polymer in einem Gemisch aus Wasser und einem oder mehreren organischen Lösungsmitteln, einem organischen Lösungsmittel oder einem Gemisch aus einem oder mehreren organischen Lösungsmitteln gelöst wird.
     


    Revendications

    1. Procédé de production de lentilles de contact en silicone hydrogel avec des revêtements hydrophiles réticulés sur celles-ci, comprenant les étapes de :

    (a) obtention d'une lentille de contact en silicone hydrogel ayant des groupes amino et/ou groupes carboxyle sur et/ou à proximité de sa surface et un matériau polymère hydrophile hydrosoluble et thermiquement réticulable, dans lequel la lentille de contact en silicone hydrogel comprend des groupes amino ou des groupes carboxyle ou les deux sur et/ou à proximité de la surface de la lentille de contact, le matériau polymère hydrophile comprenant (i) d'environ 20 % à environ 95 % en poids de premières chaînes de polymère dérivées d'une polyamine ou polyamidoamine fonctionnalisée par l'épichlorhydrine, (ii) d'environ 5 % à environ 80 % en poids de fragments hydrophiles ou de deuxième chaînes de polymère dérivées d'au moins un agent augmentant l'hydrophilie ayant au moins un groupe fonctionnel réactif choisi dans le groupe constitué d'un groupe amino, un groupe carboxyle, un groupe thiol, et une combinaison de ceux-ci, et (iii) des groupes azétidinium positivement chargés qui font partie des premières chaînes de polymère ou des groupes pendants ou terminaux liés de façon covalente aux premières chaînes de polymère, dans lequel les fragments hydrophiles ou deuxièmes chaînes de polymère sont liés de façon covalente aux premières chaînes de polymère par l'intermédiaire d'une ou plusieurs liaisons covalentes formées chacune entre un groupe azétidinium de la polyamine ou polyamidoamine fonctionnalisée par l'épichlorhydrine et un groupe amino, carboxyle ou thiol de l'agent augmentant l'hydrophilie ; et

    (b) chauffage de la lentille de contact en silicone hydrogel immergée dans une solution de conditionnement comprenant le matériau polymère hydrophile et au moins un agent tampon en une quantité suffisante pour maintenir un pH d'environ 6,0 à environ 8,5 et a une tonicité d'environ 200 à environ 450 milliosmol (mOsm) et une viscosité d'environ 1 centipoise à environ 20 centipoises à 25 °C dans un conditionnement de lentille et à une température d'environ 40 °C à environ 140 °C pendant une durée suffisante pour lier de façon covalente le matériau polymère hydrophile sur la surface de la lentille de contact en silicone hydrogel par l'intermédiaire de deuxièmes liaisons covalentes chacune formées entre un groupe azétidinium du matériau polymère hydrophile et l'un des groupes fonctionnels réactifs sur et/ou à proximité de la surface de la lentille de contact, de façon à former un revêtement hydrophile réticulé sur la lentille de contact en silicone hydrogel,

    (c) ajout d'un composant contenant des groupes polyazétidinium dans la solution de conditionnement avec la lentille de contact en silicone de l'étape (b), le composant contenant des groupes polyazétidinium comprenant au moins deux groupes choisis dans le groupe constitué de la formule (II), la formule (III) et des mélanges de celles-ci :



    dans lesquelles : R1 et R2 sont indépendamment un groupe alkylène contenant 1 à 6 atomes de carbone ; X est un contre-ion anionique ; Y1, Y2 et Y3 sont chacun indépendamment choisis dans le groupe constitué d'hydrogène, hydroxyle, halogéno, alcoxy, alkyle, amino, carboxy, acétoxy, cyano et sulfhydryle ; et Y4 est un groupe de terminaison de chaîne, choisi dans le groupe constitué d'hydrogène, alkyle, alcoxy et acyloxy ;

    (d) scellement du conditionnement de lentille avec la lentille de contact et la solution de conditionnement de l'étape (c)

    (e) réduction de la concentration de groupes amino et/ou groupes carboxyle sur et/ou à proximité de la lentille de contact en silicone hydrogel par autoclavage du conditionnement avec la lentille de contact et la solution de revêtement de conditionnement de l'étape (d) dans celui-ci et induction d'une réaction entre les groupes azétidinium du composant contenant des groupes polyazétidinium et de groupes amino et/ou groupes carboxyle résiduels sur et/ou la surface de la lentille de contact en silicone hydrogel immergée dans la solution de revêtement de conditionnement, la réduction de la concentration de groupes carboxyle sur et/ou à proximité de la lentille de contact en silicone hydrogel de l'étape (e) étant caractérisée par une absorption de conservateurs positivement chargés réduite d'au moins 20 % par rapport à la lentille de contact en silicone hydrogel de l'étape (b).


     
    2. Procédé de la revendication 1, dans lequel le composant contenant des groupes polyazétidinium a une plage de viscosité en solution de 10 à 200 m.Pa.s à 23 % de matières solides.
     
    3. Procédé de la revendication 2, dans lequel le composant contenant des groupes polyazétidinium a une plage de viscosité en solution de 30 à 160 m.Pa.s à 23 % de matières solides.
     
    4. Procédé de la revendication 3, dans lequel le composant contenant des groupes polyazétidinium a une plage de viscosité en solution de 40 à 130 m.Pa.s à 23 % de matières solides.
     
    5. Procédé de l'une quelconque des revendications 1 à 4, dans lequel la solution de revêtement de conditionnement de l'étape (b) comprend de 0,01 % à 2 % en poids de matériau polymère hydrophile thermiquement réticulable.
     
    6. Procédé de l'une quelconque des revendications 1 à 5, dans lequel le composant contenant des groupes polyazétidinium est ajouté dans la solution de revêtement de conditionnement de l'étape (c) en une quantité d'environ 0,01 % à environ 5 % en poids sur la base de la quantité totale de la solution de revêtement de conditionnement.
     
    7. Procédé de l'une quelconque des revendications 1 à 6, dans lequel l'étape de chauffage est conduite par chauffage de la lentille de contact en silicone hydrogel immergée dans une solution de conditionnement dans un conditionnement de lentille scellé à une température d'environ 40 °C à environ 140 °C pendant approximativement 20 à 180 minutes et l'étape de réduction de la concentration de groupes amino et/ou groupes carboxyle sur et/ou à proximité de la lentille de contact en silicone hydrogel par autoclavage du conditionnement avec la lentille de contact et la solution de revêtement de conditionnement à une température d'environ 118 °C à environ 125 °C pendant approximativement 20 à 90 minutes.
     
    8. Procédé de la revendication 7, dans lequel l'étape de chauffage est conduite par chauffage de la lentille de contact en silicone hydrogel immergée dans une solution de conditionnement dans un conditionnement de lentille scellé à une température d'environ 75 °C à environ 95 °C pendant approximativement 20 à 180 minutes et l'étape de réduction de la concentration de groupes amino et/ou groupes carboxyle sur et/ou à proximité de la lentille de contact en silicone hydrogel par autoclavage du conditionnement avec la lentille de contact et la solution de revêtement de conditionnement à une température d'environ 118 °C à environ 125 °C pendant approximativement environ 118 °C à environ 125 °C pendant approximativement 20 à 40 minutes.
     
    9. Procédé de l'une quelconque des revendications 1 à 8, dans lequel l'agent augmentant l'hydrophilie est un polymère hydrophile ayant un ou plusieurs groupes amino, carboxyle et/ou thiol, et la teneur en motifs monomères ayant un groupe amino, carboxyle ou thiol dans le polymère hydrophile en qu'agent augmentant l'hydrophilie est inférieure à environ 40 % en poids sur la base du poids total du polymère hydrophile.
     
    10. Procédé de l'une quelconque des revendications 1 à 9, dans lequel le poids moléculaire moyen en poids Mw du polymère hydrophile ayant au moins un groupe amino, carboxyle ou thiol est d'environ 500 à environ 1 000 000 daltons.
     
    11. Procédé de l'une quelconque des revendications 1 à 10, dans lequel la lentille de contact en silicone hydrogel comprend un revêtement de base réactif comprenant des groupes amino et/ou groupes carboxyle.
     
    12. Procédé de la revendication 11, dans lequel le revêtement de base réactif comprend au moins une couche d'un polymère réactif ayant des groupes amino et/ou groupes carboxyle pendants et est obtenu par mise en contact de la lentille de contact en silicone hydrogel avec une solution du polymère réactif, dans lequel le polymère réactif est : un homopolymère de (méth) acrylamide d'amino-(alkyle en C1 à C4), (méth) acrylate d'amino-(alkyle en C1 à C4), (méth) acrylamide de (alkyle en C1 à C4) amino-(alkyle en C1 à C4), (méth) acrylate de (alkyle en C1 à C4) amino-(alkyle en C1 à C4), allylamine, ou vinylamine ; polyéthylénimine ; un alcool polyvinylique avec des groupes amino pendants ; un poly(acide acrylique) linéaire ou ramifié ; un homopolymère d'acide (alkyle en C1 à C12) acrylique ; un copolymère de (méth) acrylamide d'amino-(alkyle en C2 à C4), (méth) acrylate d'amino-(alkyle en C2 à C4), (méth) acrylamide de (alkyle en C1 à C4) amino-(alkyle en C2 à C4), (méth) acrylate de (alkyle en C1 à C4) amino-(alkyle en C2 à C4), acide acrylique, acide (alkyle en C1 à C12) acrylique, acide maléique et/ou acide fumarique, avec au moins un monomère vinylique hydrophile non réactif ; une cellulose contenant des groupes carboxyle ; un hyaluronate ; le sulfate de chondroïtine ; le poly(acide glutamique) ; le poly(acide aspartique) ; ou des combinaisons de ceux-ci.
     
    13. Procédé de la revendication 12, dans lequel le polymère réactif pour former un revêtement de base est le poly(acide acrylique), le poly(acide méthacrylique), le poly(acide N,N-2-acrylamidoglycolique), le poly[acide (méth) acrylique-co-acrylamide], le poly[acide (méth) acrylique-co-vinylpyrrolidone], le poly[acide (méth) acrylique-co-acétate de vinyle], la polyéthylénimine (PEI), un homo- ou copolymère de chlorhydrate de polyallylamine (PAH), homo- ou copolymère de polyvinylamine, ou des combinaisons de ceux-ci.
     
    14. Procédé de la revendication 12 ou 13, dans lequel le poids moléculaire moyen en poids Mw d'un réactif polymère pour former un revêtement de base réactif est d'au moins environ 10 000 daltons.
     
    15. Procédé de la revendication 14, dans lequel le poids moléculaire moyen en poids Mw d'un réactif polymère pour former un revêtement de base réactif est d'environ 10 000 à 1 000 000 daltons.
     
    16. Procédé de l'une quelconque des revendications 12 à 15, dans lequel le réactif polymère est dissous dans un mélange d'eau et un ou plusieurs solvants organiques, un solvant organique, ou un mélange d'un ou plusieurs solvants organiques.
     






    Cited references

    REFERENCES CITED IN THE DESCRIPTION



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    Patent documents cited in the description