RU2753181C1 - Silicone hydrogel lenses with water-rich surfaces - Google Patents

Abstract

FIELD: ophthalmology.SUBSTANCE: invention relates to the field of ophthalmology and concerns a hydrated contact lens. The lens has an outer surface, an opposing back surface, and a layered structural configuration ranging from the front surface to the back surface. The layered structural configuration includes the front outer hydrogel layer having the first water content, the inner layer having the second water content, and the rear outer hydrogel layer having the third water content, with the first and third water content being greater than the second water content.EFFECT: increasing oxygen permeability of the lens, which is necessary to ensure a healthy state of the eye cornea, and providing a soft, water-enriched smooth surface to ensure wearing comfort.25 cl, 14 dwg, 11 tbl

Description

The present invention relates generally to an ophthalmic device, preferably a silicone hydrogel contact lens, which has a structural configuration that produces a water content gradient and includes: a silicone hydrogel bulk material having a water content (designated WC _SiHy ) of about 10% to about 70 wt. %, and an outer surface layer that has a thickness of about 0.1 to about 20 microns and completely covers the silicone hydrogel bulk material and consists of a hydrogel material, completely or essentially free of silicon and having a high water content, characterized by a swelling ratio of water of at least about 100% if WC _SiHy ≤45%, or a swelling ratio in water of at least about [120⋅WC _SiHy / (1-WC _SiHy )]% if WC _SiHy > 45% when measured with AFM over the cross section of a silicone hydrogel contact lens in a fully hydrated state.

LEVEL OF TECHNOLOGY

Silicone hydrogel (SiHy) contact lenses are widely used to correct many different vision defects. They are made from a hydrated crosslinked polymer material that contains silicon and some water in the polymer matrix in equilibrium. According to the FDA contact lens classification, hydrogel contact lenses are generally divided into two main categories: low water contact lenses (containing less than 50% water) and high water contact lenses (containing more than 50% water). For SiHy contact lenses, the high oxygen permeability required for a contact lens to have minimal detrimental effects on corneal health is provided by the inclusion of silicon rather than by increasing the water content of the crosslinked polymer material. As a consequence, unlike conventional hydrogel contact lenses, SiHy contact lenses can have a low water content and at the same time have a relatively high oxygen permeability (Dk), for example, Focus® Night & Day®, available from the US Vision Corporation (about 23.5 % H ₂ O and Dk ~ 140 bbl; Air Optix®, available from the U.S. Vision Corporation (about 33% H ₂ O and Dk ~ 110 barrels); PureVision®, available from Bausch & Lomb (about 36% H ₂ O and Dk ~ 100 bbl); Acuvue® Oasys® from Johnson & Johnson (about 38% H ₂ O, Dk ~ 105 bbl); Acuvue® Advance® from Johnson & Johnson (about 47% H ₂ O, Dk ~ 65 barrels); Acuvue® TruEye ™, available from Johnson & Johnson (about 46% H ₂ O, Dk ~ 100 bbl); Biofinity®, available from CooperVision (about 48% H ₂ O, Dk ~ 128 barrels); Avaira ™, available from CooperVision (approximately 46% H ₂ O, Dk ~ 100 bbl); and PremiO ™ from Menicon (about 40% H ₂ O, Dk ~ 129 bbl).

The water in a SiHy contact lens can provide the necessary softness that allows the SiHy lens to be worn for long enough periods of time and provides patient benefits, including sufficient initial comfort (i.e. immediately after lens insertion), a relatively short adaptation period for the patient to get used to. to the lens, and / or proper lens fit. A high water content is desirable for making SiHy contact lenses with biocompatibility and comfort. However, there is a limit to the amount of water (estimated to be 80%) that a SiHy contact lens can contain while maintaining sufficient mechanical strength and rigidity for a contact lens such as conventional hydrogel contact lenses. In addition, high water content can also lead to undesirable consequences. For example, the oxygen permeability of a SiHy contact lens may deteriorate with increasing water content. In addition, a high water content in a SiHy lens can lead to more dehydration in the eye and dehydration-induced discomfort when wearing, since a SiHy contact lens with a high water content can reduce the limited supply of tear fluid (water) to the eye. It is assumed that dehydration in the eye may be due to evaporation (i.e. water loss) from the front surface of the contact lens, and this water loss is mainly controlled by the diffusion of water from the back surface to the front surface and that the diffusion rate is almost proportional to the water content of the bulk lens material. in equilibrium (L. Jones et al., Contact Lens & Anterior Eye 25 (2002) 147-156, which is incorporated herein by reference in its entirety).

The inclusion of silicon in a contact lens material also has an undesirable effect on the biocompatibility of a contact lens because silicon is hydrophobic and tends to migrate to the lens surface when exposed to air. Therefore, surface modification is usually required for SiHy contact lenses to eliminate or minimize exposure to the silicone contact lens and to maintain a hydrophilic surface, including, for example, different plasma treatments (e.g. Focus® Night & Day® and Air Optix® from by Vision Corporation, USA; PureVision® by Bausch &Lomb; and PremiO ™ by Menicon); internal wetting agents physically and / or chemically incorporated into the SiHy polymer matrix (eg, Acuvue® Oasys®, Acuvue® Advance® and Acuvue® TruEye ™ from Johnson &Johnson; Biofinity® and Avaira ™ from CooperVision). While surface modification techniques used to make commercially available SiHy lenses can produce new (unused) SiHy lenses that have reasonably hydrophilic surfaces, SiHy lenses worn in the eye can contain dry patches and / or hydrophobic patches due to exposure to air, shear effects of the eyelids, migration of silicon and / or the inability to completely prevent exposure to silicone. These dry areas and / or hydrophobic surface areas are non-wetting and are capable of adsorbing lipids or proteins from the environment of the eyes, which can adhere to the eyes, resulting in patient discomfort.

Therefore, there is still a need for SiHy contact lenses with hydrophilic surfaces that are durable hydrophilicity, wettability and surface smoothness that can be worn in the eyes all day long.

SUMMARY OF THE INVENTION

The present invention can satisfy the need for SiHy contact lenses having hydrophilic surfaces that are consistently hydrophilic, surface wettable, and smooth in the eyes all day long.

One aspect of the present invention is a hydrated silicone hydrogel contact lens that includes: an anterior (convex) surface and an opposing posterior (concave) surface; and a layered structural configuration ranging from anterior surface to a posterior surface, where the layered structural configuration includes a front outer hydrogel layer, an inner layer of a silicone hydrogel material, and a rear outer hydrogel layer, where the silicone hydrogel material has an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90 barrels, most preferably at least about 110 barrels, and a first water content (referred to as WC _SiHy ) of about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about 10% to about 60%, even more preferably from about 15% to about 55%, most preferably from about 15% to about 50% by weight. %, where the front and back hydrogel layers have a substantially constant thickness and are combined at the outer edge of the contact lens, completely covering the inner layer of the silicone hydrogel material, where the front and back hydrogel layers independently have a second water content exceeding WC _SiHy , characterized by or a water swelling ratio (referred to as WSR) of at least about 100% (preferably at least about 150%, more preferably at least about 200%, even more preferably at least about 250%, most preferably at least about 300%) if WC _SiHy ≤45%, or a water swelling ratio of at least about [120⋅WC _SiHy / (1-WC _SiHy )]% (preferably [130⋅WC _SiHy / (1-WC _SiHy )]%, more preferably [140⋅WC _SiHy / (1-WC _SiHy )]%, even more preferably [150⋅WC _SiHy / (1-WC _SiHy )]%) if WC> 45%, where the thickness of each front and back outer hydrogel layers equal to about 0.1 microns m to about 20 μm, preferably from about 0.25 μm to about 15 μm, more preferably from about 0.5 μm to about 12.5 μm, even more preferably from about 1 μm to about 10 μm (as measured by atomic cross-sectional force microscopy from the back surface to the front surface of a silicone hydrogel contact lens in a fully hydrated state).

), где задняя наружная зона обладает средним модулем задней поверхности (обозначенным как

), где внутренняя зона обладает средним модулем внутренней поверхности (обозначенным как

), где по меньшей мере один из

и

составляет не менее примерно 20%, предпочтительно не менее примерно 25%, более предпочтительно не менее примерно 30%, еще более предпочтительно не менее примерно 35%, наиболее предпочтительно не менее примерно 40%.Another aspect of the present invention is a hydrated silicone hydrogel contact lens. The hydrated silicone hydrogel contact lens of the present invention includes: a silicone hydrogel material as a bulk material, an anterior surface and an opposing posterior surface; wherein the contact lens has an oxygen permeability of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 bbl / mm, and a cross-sectional modulus profile that includes the shortest the lines between the outer and inner surfaces on the cross-sectional surface of the contact lens, the front outer zone including the front surface and the region near it, the inner zone including the center of the shortest line and the region near it, and the posterior outer zone, including the back surface and the region near it, where the anterior outer zone has a middle modulus of the anterior surface (designated as

), where the posterior outer zone has a middle modulus of the posterior surface (denoted as

), where the inner zone has an average modulus of the inner surface (denoted as

), where at least one of

and

is at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, most preferably at least about 40%.

Another aspect of the present invention is a hydrated silicone hydrogel contact lens. The hydrated silicone hydrogel contact lens of the present invention includes: a silicone hydrogel material as a bulk material, an anterior surface and an opposing posterior surface; wherein the contact lens has (1) an oxygen permeability of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 bbl / mm, and (2) a surface smoothness of a critical coefficient of friction (designated as FCC) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, where the front and rear surfaces have a low surface concentration of negatively charged groups, including carboxy groups, characterized by adhesion of no more than about 200 preferably no more than about 160, more preferably no more than about 120, even more preferably no more than about 90, most preferably no more than about 60 positively charged particles in a positively charged particle adhesion study.

These and other aspects of the present invention, including various preferred embodiments in any combination, will become apparent from the following description of the preferred embodiments presented. The detailed description is mainly illustrative of the present invention and does not limit the scope of the present invention, which is defined by the appended claims and their equivalents. It should be obvious to a person skilled in the art that numerous changes and modifications of the present invention can be made without departing from the spirit and scope of the new concepts of description.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic cross-sectional view of the structural configuration of a SiHy contact lens according to a preferred embodiment of the present invention.

FIG. 2 is a schematic sectional view of the structural configuration of a SiHy contact lens according to another preferred embodiment of the present invention.

FIG. 3 shows the profiles of the fluorescence intensity over the sections of the SiHy contact lens, obtained using confocal laser fluorescence microscopy.

FIG. 4 shows SEM (Scanning Electron Microscopy) images of a SiHy contact lens of the present invention in a freeze-dried condition.

FIG. 5 is a schematic representation of a setup for a tilted plate technique according to a preferred embodiment.

FIG. 6 shows optical microscope images of contact lenses with various coatings after immersion in a dispersion of positively charged particles (DOWEX ™ 1 × 4 20-50 mesh resin).

FIG. 7 schematically shows how to vertically fasten in a metal clip a section of a SiHy contact lens of the present invention for AFM examination.

FIG. 8 is an AFM (atomic force microscopy) image of a portion of a cross-section of a SiHy contact lens in a fully hydrated state (in phosphate buffered saline, pH ~ 7.3) in accordance with a preferred embodiment of the present invention.

FIG. 9 shows the modulus profile of a cross-sectional surface modulus of a SiHy contact lens of the present invention in a fully hydrated state (in phosphate-buffered saline, pH ~ 7.3) along the two shortest lines between the anterior and posterior surfaces on the cross-sectional surface of a SiHy contact lens. corresponding to a preferred embodiment of the present invention, the described dependence of the deflection of the cantilever on the distance.

DETAILED DESCRIPTION OF EMBODIMENTS

Embodiments of the present invention are described in detail below. It should be apparent to those skilled in the art that various changes and modifications can be made to the present invention without departing from the scope and spirit of the present invention. For example, features illustrated or described as part of one embodiment can be used in another embodiment and obtain yet another embodiment. Thus, the present invention is intended to include all such changes and modifications that fall within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present invention are disclosed in the following detailed description or are obvious from it. One of ordinary skill in the art should understand that the discussion presented is only a description of exemplary embodiments and is not intended to be limiting on the broader aspects of the present invention.

Unless otherwise indicated, all technical and scientific terms used in the present invention have the same meanings as commonly known to one of ordinary skill in the art to which the present invention belongs. Typically, the nomenclature used in the present invention and laboratory procedures are well known and commonly used in the art. For these procedures, conventional techniques are used, such as those described in the art and in various general literature. If the term is used in the singular, then the authors of the present invention also assume the plural of this term. The nomenclature used in the present invention and the laboratory procedures described below are well known and commonly used in the art.

When used in this application, the term "silicone hydrogel contact lens" means a contact lens that includes a silicone hydrogel material.

When used in this application, the term "hydrogel" or "hydrogel material" means a crosslinked polymer material that is insoluble in water and may contain in its polymer matrix at least 10 wt. % water when fully hydrated.

When used in this application, the term "non-silicone hydrogel" means a hydrogel that theoretically does not contain silicon.

When used in this application, the term "silicone hydrogel" means a hydrogel containing silicon. A silicone hydrogel is typically prepared by copolymerizing a polymerizable composition containing at least one silicon-containing vinyl monomer or at least one silicon-containing vinyl macromer or at least one silicon-containing prepolymer containing ethylenically unsaturated groups.

When used in this application, the term "vinyl monomer" means a compound that contains one single ethylenically unsaturated group and can be actinically or thermally polymerized.

и/или

); аллил, винил (

), стиролил или другие содержащие С=С группы.When used in this application, the term "olefinically unsaturated group" or "ethylenically unsaturated group" i is used in the present invention in a broad sense and includes any groups containing at least one group> C = C <. Typical ethylenically unsaturated groups include, without limitation, (meth) acryloyl (

and / or

); allyl, vinyl (

), styrene or other C = C groups.

When used in this application, the term "(meth) acrylamide" means methacrylamide and / or acrylamide.

When used in this application, the term "(meth) acrylate" means methacrylate and / or acrylate.

When used in this application, the term "hydrophilic vinyl monomer" means a vinyl monomer, which in the form of a homopolymer usually forms a polymer that is soluble in water or can absorb at least 10 wt. % water.

When used in this application, the term "hydrophobic vinyl monomer" means a vinyl monomer, which in the form of a homopolymer usually forms a polymer that is insoluble in water and can absorb less than 10 wt. % water.

As used herein, the term "macromer" or "prepolymer" means a medium to high molecular weight compound or polymer that contains two or more ethylenically unsaturated groups. Medium and high molecular weight usually means an average molecular weight in excess of 700 Da.

When used in this application, the term "crosslinker" means a compound containing at least two ethylenically unsaturated groups. "Crosslinker" means a crosslinker having a molecular weight of about 700 Da or less.

When used in this application, the term "polymer" means a material formed by polymerization / crosslinking of one or more monomers or macromers or prepolymers.

When used in this application, the term "molecular weight" of a polymeric material (including monomeric or macromeric materials) means the weight average molecular weight, unless specifically indicated otherwise, or unless the study regimes indicate otherwise.

When used in this application, the term "amino group" means a primary or secondary amino group of the formula —NHR ′, in which R ′ is hydrogen or a C ₁ -C ₂₀ unsubstituted or substituted, linear or branched alkyl group, unless specifically indicated otherwise.

As used herein, the term "epichlorohydrin-functionalized polyamine" or "epichlorohydrin-functionalized polyamidoamine" means a polymer obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a significant portion of the amino groups of the polyamine or polyamidoamine to azetidinium groups.

.When used in this application, the term "azetidinium group" means a positively charged group of the formula

...

When used in this application, the term "thermally crosslinkable" in relation to a polymeric material or functional group means that a polymeric material or functional group can undergo a crosslinking (or combination) reaction with another material or functional group at a relatively elevated temperature (from about 40 ° C to about 140 ° C), and the polymeric material or functional group cannot enter into 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, more preferably at about 25 ° C) to a detectable extent (i.e., more than about 5%) over a period of about 1 hour.

, в которой n является целым числом, равным от 1 до 5, и R₁, R₂ и R₃ независимо друг от друга обозначают C₁-C₈ алкил или C₁-C₈ гидроксиалкил.When used in this application, the term "phosphorylcholine" means a zwitterionic group of the formula

in which n is an integer from 1 to 5 and R ₁ , R ₂ and R _{3 are} independently C ₁ -C ₈ alkyl or C ₁ -C ₈ hydroxyalkyl.

When used in this application, the term "reactive vinyl monomer" means a vinyl monomer containing a carboxy group or an amino group (ie, a primary or secondary amino group).

When used in this application, the term "non-reactive hydrophilic vinyl monomer" means a hydrophilic vinyl monomer that does not contain any carboxy or amino group (ie, primary or secondary amino group). The non-reactive vinyl monomer may include a tertiary or quaternary amino group.

When used in this application, the term "water-soluble" in relation to a polymer means that the polymer can be dissolved in water in an amount sufficient to form an aqueous solution of the polymer having a concentration of up to about 30 wt. % at room temperature (defined above).

When used in this application, the term "water contact angle" means the average water contact angle (ie, contact angles measured by the fixed drop technique), which is obtained by averaging the measured contact angles.

As used in this application, the term "integrity" in relation to a coating on a SiHy contact lens means the degree to which a contact lens can be stained with Sudan Black dye when tested with Sudan Black staining described in Example 1. Good coating integrity on a silicone hydrogel contact lens means that Sudan black practically does not stain the contact lens.

As used in this application, the term "durability" in relation to a coating on a SiHy contact lens means that the coating on a SiHy contact lens can pass the finger rub test.

When used in this application, the term "pass the finger wipe test" or "pass the durability test" in relation to a coating on a contact lens means that after wiping the lens with fingers using the procedure described in Example 1, the contact angle of water wetting of the lens rubbed with fingers is still about 100 ° or less, preferably about 90 ° or less, more preferably about 80 ° or less, most preferably about 70 ° or less.

The intrinsic "oxygen permeability", Dk, of a material refers to the rate at which oxygen will pass through the material. When used in this application, the term "oxygen permeability (Dk)" in relation to a hydrogel (silicone or non-silicone) or contact lens means oxygen permeability (Dk), which is corrected for the surface resistance to oxygen flow due to the influence of the boundary layer, according to the methods given in the examples below. Oxygen permeability is expressed in units of barrels, where "barrers" is defined as [( ^{oxygen cm 3} ) (mm) / (cm ² ) (s) (mmHg)] × 10 ¹⁰ .

"Oxygen permeability", Dk / t, of a lens or material means the rate at which oxygen will pass through a particular lens or material having an average thickness t [in units of mm] across the area of interest. Oxygen permeability is usually expressed in units of bbl / mm, where "bbl / mm" is defined as [(cm ³ oxygen) / (cm ² ) (s) (mm Hg)] × 10 ^-9 .

The "ion permeability" of a lens correlates with the diffusion coefficient of Ionoflux. The diffusion coefficient of Ionoflux, D (in units of [mm ² / min]), is determined by applying Fick's law as follows:

D = -n '(A × dc / dx)

where: n '= ion transport rate [mol / min]; A = area of the area of the lens that is affected [mm ² ]; dc = concentration difference [mol / l]; dx = lens thickness [mm].

As used in this application, the term "ophthalmologically compatible" means a material or surface of a material that can be in direct contact with the ocular environment for an extended period of time without significant damage to the ocular environment and without significant discomfort to the user.

When used in this application, the term "ophthalmologically safe" in relation to packaging solution intended for sterilizing and storing contact lenses means that the contact lens stored in the solution is safe for direct placement in the eye without rinsing after autoclaving and that the solution is safe and comfortable enough for constant eye contact through a contact lens. The ophthalmologically safe packaging solution, after autoclaving, has a tonicity and pH that is compatible with the eye and is substantially free of eye irritants or eye cytotoxic substances in accordance with international ISO and U.S. regulations. FDA (United States Food and Drug Administration).

As used in this application, the term "cross-section" of a SiHy contact lens means a lens segment obtained by cutting with a knife or cutting tool at a near-right angle to the front and back surfaces of the lens. The person skilled in the art is well aware of how to cut by hand (ie, cut by hand) or with a Cryosta microtome or rod and a contact lens and obtain a cross section of the contact lens. The resulting section of the contact lens can be polished using ion etching or similar techniques.

JM, Almeida JB and Parafita МК in Microscopy: Science, Technology, Applications and Education, "Analysis of Surface Mechanical Properties of Unworn and Worn Silicone Hydrogel Contact Lenses Using Nanoindentation with AFM", pp. 554-559, A.

и J.

(Eds.), Formatex Research Center, Badajoz, Spain (2010), которые во всей своей полноте включены в настоящее изобретение в качестве ссылки. Следует отметить, что поверхность сечения контактной линзы, не переднюю или заднюю поверхность контактной линзы (как это проводили

JM, Almeida JB и Parafita МК в своей публикации), исследуют посредством наноиндентации с помощью АСМ. Методика наноиндентации, методика Peakforce QNM и методика гармонической квазиупругой силы описаны в публикации Kim Sweers, et al. in Nanoscale Research Letters 2011, 6:270, под названием "Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM" (которая во всей своей полноте включена в настоящее изобретение в качестве ссылки). Также следует понимать, что, если измерение поверхностного модуля упругости проводят с помощью АСМ по сечению полностью гидратированной SiHy контактной линзы от передней поверхности к объему или от объема к задней поверхности (или наоборот), то профиль модуля поверхности по сечению контактной линзы можно установить по самой короткой линии между наружной и внутренней поверхностями на поверхности сечения контактной линзы. Также следует понимать, что в хорошем приближении любое экспериментальное и непосредственно измеренное значение можно использовать для описания модуля поверхности, если измеренное значение пропорционально модулю поверхности.The terms "surface modulus", "surface softness", "surface elastic modulus", "Young's modulus of the surface" or surface compression modulus are used interchangeably herein and mean nanomechanical characteristic (elasticity) as measured by atomic force microscopy (AFM) on the surface of the material or section of the contact lens in a completely hydrated state (in a phosphate-buffered solution, pH ~ 7.3 ± 0.2) in contact mode, by the nanoindentation technique, by the Peakforce QNM technique or by the harmonic quasi-elastic force technique known to the person skilled in the art the field of technology. Jan Domke and Manfred Radmacher reported that the elastic characteristics of thin films can be investigated using ACM (Langmuir 1998, 14, 3320-3325, which is incorporated herein by reference in its entirety). Nanoindentation using AFM can be carried out according to the experimental method described in publications

JM, Almeida JB and Parafita MK in Microscopy: Science, Technology, Applications and Education, "Analysis of Surface Mechanical Properties of Unworn and Worn Silicone Hydrogel Contact Lenses Using Nanoindentation with AFM", pp. 554-559, A.

and J.

(Eds.), Formatex Research Center, Badajoz, Spain (2010), which are incorporated herein by reference in their entirety. It should be noted that the cross-sectional surface of the contact lens, not the anterior or posterior surface of the contact lens (as performed

JM, Almeida JB and Parafita MK in their publication), are investigated by means of nanoindentation using AFM. The nanoindentation technique, the Peakforce QNM technique, and the harmonic quasi-elastic force technique are described in Kim Sweers, et al. in Nanoscale Research Letters 2011, 6: 270, entitled "Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM" (which is hereby incorporated by reference in its entirety) ... It should also be understood that if the measurement of the surface modulus of elasticity is carried out using AFM over the section of a fully hydrated SiHy contact lens from the front surface to the volume or from the volume to the back surface (or vice versa), then the profile of the surface modulus along the section of the contact lens can be established by the very a short line between the outer and inner surfaces on the cross-sectional surface of the contact lens. It should also be understood that, to a good approximation, any experimental and directly measured value can be used to describe the modulus of a surface if the measured value is proportional to the modulus of the surface.

When used in this application, the term "anterior outer hydrogel layer" in relation to a SiHy contact lens of the present invention means a hydrogel layer that includes the anterior surface of a contact lens that has a substantially constant thickness (i.e., thickness variations are no more than about 10% of the average thickness of this layer), and has an average thickness of at least about 0.1 microns. The "average thickness" of the anterior outer hydrogel layer is referred to herein simply as the "thickness of the anterior outer hydrogel layer".

When used in this application, the term "posterior outer hydrogel layer" in relation to the SiHy contact lens of the present invention means the hydrogel layer that includes the posterior surface of the contact lens has a substantially constant thickness (i.e., thickness changes are no more than about 10% of the average thickness of this layer), and has an average thickness of at least about 0.1 microns. The "average thickness" of the posterior outer hydrogel layer is referred to herein simply as the "thickness of the posterior outer hydrogel layer".

When used in this application, the term "inner layer" in relation to the SiHy contact lens of the present invention means a layer that includes a central curved surface (which divides the contact lens into two parts, one containing the front surface and the second containing the back surface) and has variable thickness.

When used in this application, the term "crosslinked coating" or "hydrogel coating" is used interchangeably to describe a crosslinked polymeric material containing a three-dimensional network that can contain water when fully hydrated. The three-dimensional network of a crosslinked polymeric material can be formed by crosslinking two or more linear or branched polymers by crosslinking.

, где WSR обозначает отношение набухания в воде для переднего или заднего наружного гидрогелевого слоя, L_Wet обозначает среднюю толщину этого наружного гидрогелевого слоя SiHy контактной линзы в полностью гидратированном состоянии, измеренную с помощью АСМ по сечению SiHy контактной линзы в полностью гидратированном состоянии (т.е. в забуференном фосфатом растворе, рН ~ 7,3±0,2), и L_Dry обозначает среднюю толщину этого наружного гидрогелевого слоя SiHy контактной линзы в сухом состоянии, измеренную с помощью АСМ по сечению SiHy контактной линзы в сухом состоянии (высушенной без сохранения пористости гидрогелевого материала, например, высушенной в вакууме) и в основном в сухой атмосфере. Предполагается, что отношение набухания в воде для каждого наружного гидрогелевого слоя (SiHy контактной линзы, предлагаемой в настоящем изобретении) пропорционально содержанию воды в каждом наружном гидрогелевом слое и отношение набухания в воде, составляющее не менее примерно 100% или

(в зависимости от того, что больше, WC_SiHy обозначает содержание воды в объеме (или во внутреннем слое) силиконового гидрогелевого материала SiHy контактной линзы, предлагаемой в настоящем изобретении) может являться хорошим показателем природы наружных гидрогелевых слоев, обладающих большим содержанием воды по сравнению с объемом (или во внутреннем слое) силиконового гидрогелевого материала SiHy контактной линзы, предлагаемой в настоящем изобретении.When used in this application, the term "swelling in water" in relation to the anterior or posterior outer hydrogel layer of the SiHy hydrogel material of the contact lens of the present invention means the value determined by AFM according to the formula

where WSR denotes the water swelling ratio for the anterior or posterior outer hydrogel layer, L _Wet denotes the average thickness of this outer hydrogel layer of a SiHy contact lens in a fully hydrated state, as measured by AFM at the cross section of a SiHy contact lens in a fully hydrated state (i.e. in phosphate-buffered solution, pH ~ 7.3 ± 0.2), and L _Dry denotes the average dry thickness of this outer hydrogel layer of a SiHy contact lens, measured by AFM across the section of a SiHy contact lens in a dry state (dried without preservation porosity of the hydrogel material, for example, dried in a vacuum) and mainly in a dry atmosphere. It is assumed that the water swell ratio for each outer hydrogel layer (SiHy contact lens of the present invention) is proportional to the water content of each hydrogel outer layer and the water swell ratio of at least about 100%, or

(whichever is greater, WC _SiHy denotes the water content in the bulk (or in the inner layer) of the silicon hydrogel material SiHy of the contact lens of the present invention) can be a good indicator of the nature of the outer hydrogel layers having a higher water content compared to volume (or in the inner layer) of the silicone hydrogel material SiHy contact lens proposed in the present invention.

When used in this application, the term "reduced surface modulus" in relation to one or both of the anterior and posterior outer hydrogel layers of a SiHy contact lens of the present invention means the value calculated by the following equation

означает средний модуль поверхности заднего или переднего наружного гидрогелевого слоя, и

означает средний модуль поверхности внутреннего слоя.

и

получают из профиля модуля поверхности по сечению SiHy контактной линзы в полностью гидратированном состоянии (измеренного путем анализа механических характеристик поверхности, т.е. модуля сечения поверхности полностью гидратированной SiHy контактной линзы с помощью АСМ), как это описано выше. Предполагается, что профиль модуля поверхности по сечению (т.е. зависимость модуля поверхности от расстояния от передней или задней поверхности до второй поверхности по самой короткой линии между наружной и внутренней поверхностями на поверхности сечения SiHy линзы в полностью гидратированном состоянии) должен содержать по меньшей мере две наружные зоны (одна включает переднюю поверхность и вторая включает заднюю поверхность) и одну внутреннюю зону (соответствующую объемному силиконовому гидрогелевому материалу. Средний модуль поверхности наружной зоны (т.е. наружного гидрогелевого слоя) получают путем усреднения всех модулей поверхности наружной зоны, исключая область толщиной от примерно 1 до примерно 2 мкм между наружной зоной и внутренней зоной (т.е. в граничной области или переходной зоне и/или вблизи от них).In which RSM means the reduced modulus of the anterior or posterior outer hydrogel layer relative to the inner layer,

means the average modulus of the surface of the posterior or anterior outer hydrogel layer, and

means the average modulus of the surface of the inner layer.

and

obtained from the profile of the surface modulus of a SiHy contact lens in a fully hydrated state (measured by analyzing the mechanical characteristics of the surface, i.e., the modulus of the surface of a fully hydrated SiHy contact lens using AFM), as described above. It is assumed that the cross-sectional surface modulus profile (i.e., the dependence of the surface modulus on the distance from the front or rear surface to the second surface along the shortest line between the outer and inner surfaces on the cross-sectional surface of the SiHy lens in a fully hydrated state) should contain at least two outer zones (one includes the front surface and the other includes the back surface) and one inner zone (corresponding to the bulk silicone hydrogel material. a thickness of about 1 to about 2 microns between the outer zone and the inner zone (i.e., in the boundary region or transition zone and / or near them).

The "critical coefficient of friction" is the tangent of the critical angle, which is the largest tilt angle of the tilted plate at which the lens begins to slide over the tilted plate after being pushed, but stops or slides to the end for more than 10 s. Critical coefficient of friction (CRF) techniques are described in Example 29. The critical coefficient of friction (CRF) of a contact lens is expected to correlate with the surface smoothness of that contact lens and can be used to quantify the surface smoothness of a contact lens.

As used herein, a "positively charged particle adhesion study" means a study designed to determine the surface concentration of negatively charged groups (eg, carboxy groups) of a hydrated SiHy contact lens. The study of the adhesion of positively charged particles is carried out as follows. Aqueous dispersion of DOWEX ™ 1 × 4 20-50 mesh resins, having spherical particles of strongly basic Type I resins (styrene / divinylbenzene copolymers containing N ⁺ (CH ₃ ) ₃ Cl ^- functional groups and 4% divinylbenzene), is prepared by dispersing a certain amount DOWEX ™ 1 × 4 20-50 mesh resins in phosphate buffered saline (pH ~ 7.3) to provide a resin concentration of 5 wt. %, and then mix thoroughly by shaking or stirring, or shaking at about 1000 rpm for 10 seconds. Hydrated silicone hydrogel contact lenses are immersed in the aqueous dispersion of DOWEX ™ 1 × 4 20-50 mesh resins obtained above and mixed by vortexing at about 1000-1100 rpm for about 1 minute, then rinsed with distilled water and shaken in distilled water for about 1 min. The lenses are then placed in water in Petri dishes and images of the lenses are acquired with a Nikon optical microscope with bottom illumination. You can count the number of positively charged particles adhering to the surface of each lens. The amount of positively charged particles adhering to the lens surface is proportional to the surface concentration of negatively charged groups on the contact lens.

When used in this application, the term "carboxylic acid content" in relation to the crosslinked coating or the outer hydrogel layer of the SiHy contact lens of the present invention means the percentage by weight of carboxy groups (COOH) based on the weight of the crosslinked coating or outer hydrogel layer of the SiHy contact lens. lenses. The carboxylic acid content of the crosslinked coating or outer hydrogel layer can be estimated theoretically based on the composition of the precursors for making the crosslinked coating or outer hydrogel layer and the carboxylic acid content of each precursor.

The present invention relates to a SiHy contact lens having a layered structural configuration and an unusual water content gradient from the inside to the outside of a SiHy contact lens: a low water content in a silicone hydrogel core (or bulk material) completely enclosed by an outer (surface) hydrogel layer having high water content and appropriate thickness (not less than about 0.1 microns) and substantially free of silicon (preferably completely free of silicon); and a water content in the outer hydrogel layer that is at least about 1.2 times (or 120%), preferably at least about 1.3 times (or 130%), more preferably at least about 1.4 times (or 140%), even more preferably at least about 1.5 times (150%), most preferably at least about 2 times (or 200%) the water content of the bulk material. FIG. 1 schematically illustrates a SiHy contact lens having a layered structural configuration according to a preferred embodiment. In this preferred embodiment of the present invention, the SiHy contact lens 100 has an anterior surface (or an anterior curved or convex surface) 101 and an opposing posterior surface (or a posterior curved or concave surface) 102 that, when worn by a user, bears against the cornea of the eye. The SiHy contact lens 100 includes an inner (or middle) layer 110 and two outer layers 120. The inner layer 110 is a bulk material of the SiHy contact lens 100 and has a 3-dimensional shape very similar to the SiHy contact lens 100. The inner layer 110 is preferably made of low water content silicone hydrogel. The two outer layers 120 are substantially identical, have a substantially constant thickness and are composed of a substantially silicon-free hydrogel material (preferably silicon-free at all) with a higher water content than the inner layer 110. The two outer layers 120 are combined on the outer the edge 103 of the contact lens 100 and completely cover the inner layer 110.

A SiHy contact lens having the layered structural configuration of the present invention can provide significant advantages over prior art contact lenses. First, such a SiHy contact lens may still have high oxygen permeability, which is necessary to maintain a healthy cornea. Second, because the inner layer (bulk material) provides the bulk mechanical strength and rigidity required for a contact lens, the outer hydrogel layers may not be subject to water restrictions and may contain as much water as possible. The outer hydrogel layers themselves can give a contact lens with a super-water-rich layer or with a water content gradient in the lens's structural configuration (with the highest water content in the vicinity of the lens surface and including it and with the least water content in the lens core). Third, the SiHy contact lens having the layered structural configuration of the present invention can be slightly dehydrated in the eye, can provide less dry eye sensation, and therefore can provide improved comfort in daily wear. It is assumed that the inner layer (i.e. the bulk material of the lens), which has a low water content, will regulate (limit) the rate of diffusion of water through the lens from the rear surface to the front surface and, in turn, evaporation (water loss) on the front surface lenses. It is also contemplated that the layered structural configuration of the present invention can create an inwardly directed water content gradient (i.e., water content decreasing as it goes inward from the front surface to the lens core), which is disadvantageous for water diffusion through the lens from the rear surface. to the front surface in accordance with Fick's law of diffusion. Fourth, a SiHy contact lens having the layered structural configuration of the present invention can provide good biocompatibility because water is highly biocompatible with tear fluid and because the high water content (e.g., preferably> 75% H ₂ O) in the outer hydrogel layers is observed in and near the anterior and posterior surfaces, which are in direct contact with the eye and where biocompatibility is most important. Fifth, a high water content in the outer hydrogel layers of proper thickness can give a SiHy contact lens having a very soft surface, i.e. "water cushion". Sixth, the SiHy contact lens having the layered structural configuration of the present invention can have a very smooth surface. It is believed that the outer hydrogel layer, having a very high water content and adequate thickness, forms a hydrophilic surface that can attract tear fluid for distribution over the lens surface. It is assumed that the outer hydrogel layer, which is much softer than the bulk material of the lens (inner layer), can be highly susceptible to deformation under pressure (i.e., shear force of the eyelids) and can provide elastohydrodynamic lubrication when such SiHy is worn in the eye. contact lens. Seventh, the layered structural configuration in the SiHy contact lens of the present invention can prevent exposure to silicon. It is believed that a three-dimensional network (ie, polymer matrix) of the outer hydrogel layers, having an appropriate thickness, can enclose the silicon and prevent the migration of silicon to the lens surface. Eighth, the SiHy contact lens of the present invention can have a low surface concentration of negatively charged groups (e.g. carboxy groups) and is less prone to dirt adhesion when handled by the patient and less protein adhesion during wear (it is assumed that most of the proteins found in lacrimal fluid, positively charged).

(предпочтительно

более предпочтительно

еще более предпочтительно

если WC_SiHy > 45%, где толщина каждого наружного гидрогелевого слоя равна от примерно 0,1 мкм до примерно 20 мкм, предпочтительно от примерно 0,25 мкм до примерно 15 мкм, более предпочтительно от примерно 0,5 мкм до примерно 12,5 мкм, еще более предпочтительно от примерно 1 мкм до примерно 10 мкм (при измерении с помощью атомной силовой микроскопии по сечению от задней поверхности до передней поверхности силиконовой гидрогелевой контактной линзы в полностью гидратированном состоянии). Предпочтительно, если передняя и задняя поверхности обладают низкой поверхностной концентрацией отрицательно заряженных групп (например, карбоксигрупп), характеризующейся прилипанием не более примерно 200, предпочтительно не более примерно 160, более предпочтительно не более примерно 120, еще более предпочтительно не более примерно 90, наиболее предпочтительно не более примерно 60 положительно заряженных частиц при исследовании адгезии положительно заряженных частиц. Также предпочтительно, если гидратированная силиконовая гидрогелевая контактная линза обладает гладкостью поверхности, характеризующейся значением критического коэффициента трения (обозначенного как ККОТ), равным примерно 0,046 или менее, предпочтительно примерно 0,043 или менее, более предпочтительно примерно 0,040 или менее.One aspect of the present invention is a hydrated silicone hydrogel contact lens that includes: an anterior (convex) surface and an opposing posterior (concave) surface; and a layered structural configuration ranging from anterior surface to a posterior surface, where the layered structural configuration includes a front outer hydrogel layer, an inner layer of a silicone hydrogel material, and a rear outer hydrogel layer, where the silicone hydrogel material has an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90, most preferably at least about 110 barrels, and a first water content (referred to as WC _SiHy ) of about 10% to about 70 %, preferably from about 10% to about 65%, more preferably from about 10% to about 60%, even more preferably from about 15% to about 55%, most preferably from about 15% to about 50% by weight. %, where the anterior and posterior hydrogel layers have a substantially constant thickness and are combined at the outer edge of the contact lens, completely covering the inner layer of the silicone hydrogel material, and where the anterior and posterior hydrogel layers independently of each other have a second water content exceeding WC _SiHy , characterized by or a water swelling ratio of at least about 100% (preferably at least about 150%, more preferably at least about 200%, even more preferably at least about 250%, most preferably at least about 300%) if WC _SiHy ≤ 45%, or a water swelling ratio of at least about

(preferably

more preferably

even more preferably

if WC _SiHy > 45%, where the thickness of each outer hydrogel layer is from about 0.1 microns to about 20 microns, preferably from about 0.25 microns to about 15 microns, more preferably from about 0.5 microns to about 12.5 µm, even more preferably from about 1 µm to about 10 µm (as measured by atomic force microscopy over a section from the back surface to the front surface of the silicone hydrogel contact lens in a fully hydrated state). Preferably, the front and rear surfaces have a low surface concentration of negatively charged groups (e.g., carboxy groups) characterized by adhesion of no more than about 200, preferably no more than about 160, more preferably no more than about 120, even more preferably no more than about 90, most preferably no more than about 60 positively charged particles when studying the adhesion of positively charged particles. It is also preferred if the hydrated silicone hydrogel contact lens has a surface smoothness with a critical coefficient of friction (referred to as CCOT) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less.

In the context of the present invention, the SiHy inner layer of a contact lens is substantially the bulk of the lens material. It can be formed directly from a preformed SiHy contact lens using a surface modification procedure in which two outer hydrogel layers are applied and attached directly and / or indirectly to preformed SiHy contact lenses. The preformed SiHy contact lens can be any commercially available SiHy lens such as one described above. Alternatively, preformed SiHy can be made by any technique well known to one of ordinary skill in the art. For example, preformed contact lenses can be made in a conventional rotating casting mold, as described, for example, in U.S. Pat. No. 3408429, or the static mold casting method described in U.S. patents. Ms 4347198; 5508317; 5583463; 5789464 and 5849810, or by cutting off the silicone hydrogel protrusions on a lathe, as is done in the manufacture of custom contact lenses. When molded, the lens composition is typically placed in molds and cured (i.e., polymerized and / or stitched) in contact lens molds. For the manufacture of preformed SiHy contact lenses, a SiHy lens composition for injection molding or for making SiHy rods used in turning contact lenses on a lathe typically comprises at least one component selected from the group consisting of a silicon-containing vinyl monomer, a silicon-containing vinyl macromer, silicon-containing prepolymer, hydrophilic vinyl monomer, hydrophobic vinyl monomer, crosslinking agent (compound having a molecular weight of about 700 Da or less and containing at least two ethylenically unsaturated groups), free radical initiator (photoinitiator or thermal initiator), hydrophilic / prepolymer and combinations thereof, as is well known to the person skilled in the art. The SiHy contact lens composition may also include other necessary components known to a person skilled in the art, such as, for example, a UV absorbing reagent, a visible tinting agent (for example, dyes, pigments or mixtures thereof), antimicrobial agents (for example, preferably silver nanoparticles), a biologically active agent, leachable lubricants, leachable tear stabilizing agents and mixtures thereof, as known to the person skilled in the art. The fabricated preformed SiHy contact lenses can then be subjected to extraction with an extracting solvent to remove uncured components from the fabricated lenses and for hydration, as known to one of ordinary skill in the art. In addition, the preformed SiHy contact lens may be a colored contact lens (ie, a SiHy contact lens having at least one color image printed thereon, as is well known to a person skilled in the art).

Any suitable silicon-containing vinyl monomers can be used in the present invention. Examples of preferred silicon-containing vinyl monomers include, without limitation, N- [tris (trimethylsiloxy) silylpropyl] - (meth) acrylamide, N- [tris (dimethylpropylsiloxy) silylpropyl] - (meth) acrylamide, N- [tris (dimethylphenylsiloxy) silyl meth) acrylamide, N- [tris (dimethylethylsiloxy) silylpropyl] (meth) acrylamide, N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) -2-methylacrylamide; N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) acrylamide; N, N-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] -2-methylacrylamide; N, N-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] acrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) -2-methylacrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) acrylamide; N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] -2-methylacrylamide; N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] acrylamide; N- [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] -2-methylacrylamide; N- [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] acrylamide; N, N-bis [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] -2-methylacrylamide; N, N-bis [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] acrylamide; 3-methacryloxypropylpentamethyldisiloxane, tris (trimethylsilyloxy) silylpropyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy) propylbis (trimethylsiloxy) methylsilane), (3-methacryloxy-2-hydroxypropyloxy) propyl-3-yloxy- (2-hydroxyethoxy) -propyloxy) propylbis (trimethylsiloxy) methylsilane, N-2-methacryloxyethyl-O- (methylbis-trimethylsiloxy-3-propyl) silyl carbamate, 3- (trimethylsilyl) propylvinyl carbonate, 3- (trimethylsilyl) propylvinyl carbonate, 3- (trimethylsilyl) methylsilane , 3- [tris (trimethylsiloxy) silyl] propylvinyl carbamate, 3- [tris (trimethylsiloxy) silyl] propyl allyl carbamate, 3- [tris (trimethylsiloxy) silyl] propyl vinyl carbonate, tert-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethylvinyl carbonate, and trimethylsilylmethylvinyl carbonate). Particularly preferred siloxane (meth) acrylamide-containing monomers of formula (1) are N- [tris (trimethylsiloxy) silylpropyl] acrylamide, TRIS, N- [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] acrylamide, or their combinations.

A class of preferred silicon-containing vinyl monomers or macromers are polysiloxane-containing vinyl monomers or macromers. Examples of such polysiloxane-containing vinyl monomers or macromers are monomethacrylated or monoacrylated polydimethylsiloxanes having different molecular weights (for example, having a mono-3-methacryloxypropyl end group, a monobutyl end group containing propydimethylsiloxane, or mono-acrylated polydimethylsiloxane a group containing a monobutyl end group (polydimethylsiloxane); dimethacrylated or diacrylated polydimethylsiloxanes having different molecular weights; vinyl carbonate-terminated polydimethylsiloxanes; a vinylcarbamate-terminated polydimethylsiloxane; vinyl-terminated polydimethylsiloxanes having different molecular weights; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; acrylate-terminated polydimethylsiloxanes; methacrylate-terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N, N, N ', N'-tetrakis (3-methacryloxy-2-hydroxypropyl) -alpha, omega-bis-3-aminopropyl-polydimethylsiloxane; polysiloxanylalkyl (meth) acrylic monomers; a siloxane-containing macromer selected from the group consisting of Macromer A, Macromer B, Macromer C, and Macromer D described in US Pat. No. 5,760,100 (which is incorporated herein by reference in its entirety); reaction products of glycidyl methacrylate with polydimethylsiloxanes containing amino groups; hydroxy-containing siloxane-containing vinyl monomers or macromers; polysiloxane-containing macromers disclosed in U.S. No. 4136250, 4153641, 4182822, 4189546, 4343927, 4254248, 4355147, 4276402, 4327203, 4341889, 4486577, 4543398, 4605712, 4661575, 4684538, 4703097, 4833218, 5086105, 4954517 5039761, 5346946, 5358995, 5387632, 5416132, 5451617, 5486579, 5962548, 5981675, 6039913 and 6762264 (which are hereby incorporated by reference in their entirety); polysiloxane-containing macromers disclosed in U.S. Nos. 4259467, 4260725 and 4261875 (which in their entirety are included in the present invention by reference). You can also use di- and triblock macromers containing polydimethylsiloxane and polyalkylene oxides. For example, methacrylate-terminated polyethylene oxide-block-polydimethylsiloxane-block-polyethylene oxide can be used to increase oxygen permeability. Suitable monofunctional hydroxy-containing siloxane-containing vinyl monomers / macromers and suitable multifunctional hydroxy-group-containing siloxane-containing vinyl monomers / macromers are available from Gelest, Inc., Morrisville, PA.

Another class of preferred silicon-containing macromers are silicon-containing prepolymers containing hydrophilic segments and hydrophobic segments. Any suitable silicon-containing prepolymers containing hydrophilic segments and hydrophobic segments can be used in the present invention. Examples of such silicon-containing prepolymers include those described in co-owned US patents No. 6039913, 7091283, 7268189 and 7238750, 7521519; in jointly owned patent application publications US No. US 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US 2008-0234457 A1, US 2008-0231798 A1 and in jointly owned patent applications US Nos. 61/180449 and 61/180453; which are all incorporated by reference in their entirety.

Examples of preferred hydrophilic vinyl monomers are N, N-dimethylacrylamide (DMA), N, N-dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-) [methyl tris] ( -acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone , 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2 -pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene -2-pyrrolidone, 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxypropyl methacrylate hydrochloride, aminopropyl methacrylate hydroxymethylacrylate (NVP), allyl alcohol, vinylpyridine, C ₁ -C ₄ -alkox polyethylene glycol (meth) acrylate having a weight average molecular weight of up to 1500, methacrylic acid, N-vinylformamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, N-vinyl caprolactam and mixtures thereof.

Examples of preferred hydrophobic vinyl monomers include methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, vinyl acetate, vinyl propionate, vinyl butyryl-butyrylone, styrene, vinyl methacrylonitrile, vinyl toluene, vinyl ethyl ether, perfluorohexylethylthiocarbonylaminoethyl methacrylate, isobornyl methacrylate, trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl methacrylate.

Examples of preferred crosslinking reagents include, without imposing tetraetilenglikoldiakrilat limitations trietilenglikoldiakrilat, etilenglikoldiatsilat, diethylene glycol, tetraetilenglikoldimetakrilat, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, pentaeritrittetrametakrilat, bisphenol A dimethacrylate, vinyl methacrylate, etilendiamindimetilakrilamid, etilendiamindiakrilamid, glitserindimetakrilat, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1, 1 , 3-bis (N-methacrylamidopropyl) -1,1,3,3-tetrakis- (trimethylsiloxy) disiloxane, 1,3-bis (methacrylamidobutyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1 , 3-bis (acrylamidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacryloxyethylureidopropyl) -1,1 , 3,3-tetrakis (trimethylsiloxy) disiloxane, and combinations thereof. The preferred crosslinking reagent is tetra (ethylene glycol) diacrylate, tri (ethylene glycol) diacrylate, ethylene glycol diacrylate, di (ethylene glycol) diacrylate, methylene bisacrylamide, triallyl isocyanurate, or triallyl cyanurate. The amount of crosslinking agent used is expressed in terms of weight based on the total polymer and is preferably in the range of about 0.05% to about 4%, and more preferably in the range of about 0.1% to about 2%.

Examples of suitable thermal initiators include, but are not limited to, 2,2'-azobis (2,4-dimethylpentanenitrile), 2,2'-azobis (2-methylpropanenitrile), 2,2'-azobis (2-methylbutanenitrile), peroxides such as benzoyl peroxide and the like. The preferred thermal initiator is 2,2'-azobis (isobutyronitrile) (AIBN).

Suitable photoinitiators are benzoin methyl ester, diethoxyacetophenone, benzoylphosphine oxide, 1-hydroxycyclohexylphenyl ketone and Darocur and Irgacur type photoinitiators, preferably Darocur 1173® and Darocur 2959®. Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzoyl diphenylphosphine oxide; bis- (2,6-dichlorobenzoyl) -4-N-propylphenylphosphine oxide; and bis- (2,6-dichlorobenzoyl) -4-H-butylphenylphosphine oxide. Also suitable are reactive photoinitiators, which can be included, for example, in the macromer, or can also be used as a special monomer. Examples of reactive photoinitiators are those disclosed in EP 632329, which is incorporated herein by reference in its entirety. The polymerization can then be initiated using actinic radiation, for example light, in particular UV radiation of a suitable wavelength. Spectral conditions can be appropriately adjusted, if appropriate, by adding suitable photosensitizers.

Any suitable polymerizable UV absorbing reagent can be used in the present invention. The polymerizable UV absorbing reagent contains a benzotriazole moiety or a benzophenone moiety. Examples of preferred polymerizable UV absorbers include, without limitation, 2- (2-hydroxy-5-vinylphenyl) -2H-benzotriazole, 2- (2-hydroxy-5-acrylyloxyphenyl) -2H-benzotriazole, 2- (2-hydroxy- 3-methacrylamidomethyl-5-tert-octylphenyl) benzotriazole, 2- (2'-hydroxy-5'-methacrylamidophenyl) -5-chlorobenzotriazole, 2- (2'-hydroxy-5'-methacrylamidophenyl) -5-methoxybenzotriazole, 2- (2'-hydroxy-5'-methacryloxypropyl-3'-tert-butylphenyl) -5-chlorobenzotriazole, 2- (2'-hydroxy-5'-methacryloxyethylphenyl) benzotriazole, 2- (2'-hydroxy-5'-methacryloxypropylphenyl ) benzotriazole, 2-hydroxy-4-acryloxyalkoxybenzophenone, 2-hydroxy-4-methacryloxyalkoxybenzophenone, allyl-2-hydroxybenzophenone, 2-hydroxy-4-methacryloxybenzophenone.

A biologically active agent is any compound that can prevent an eye disease or ameliorate the symptoms of an eye disease. The biologically active agent can be a drug, an amino acid (eg, taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid, or any combination thereof. Examples of drugs useful in the present invention include, but are not limited to, rebamipide, ketotifen, olaptidine, cromoglycollate, cyclosporin, nedocromil, levocarbastine, lodoxamide, ketotifen, or a pharmaceutically acceptable salt or ester thereof. Other examples of biologically active agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxy acids (for example, glycolic, lactic, malic, tartaric, mandelic and citric acids and their salts, etc.), linolenic and gamma linolenic acid and vitamins (for example, B5, A, B6, etc.).

Examples of leachable lubricants include, without limitation, mucin-like substances (eg, polyglycolic acid) and non-crosslinkable hydrophilic polymers (ie, without ethylenically unsaturated groups). Any hydrophilic polymers or copolymers that do not contain any ethylenically unsaturated groups can be used as leachable lubricants. Preferred examples of non-crosslinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohols (PVA), polyamides, polyimides, polylactone, vinyl lactam homopolymer, copolymer of at least one vinyl lactam in the presence or absence of one or more hydrophilic vinyl comonomers, acrylamide homopolymer, or methacrylamide, copolymer of acrylamide or methacrylamide with one or more hydrophilic vinyl monomers, polyethylene oxide (i.e. polyethylene glycol (PEG)), polyoxyethylene derivative, poly-NN-dimethylacrylamide, polyacrylic acid, poly-2-ethyloxazoline, heparidic polysaccharides their mixtures. The weight average molecular weight M _{w of the} non-crosslinkable hydrophilic polymer is preferably 5,000 to 100,000.

Examples of leachable tear stabilizing agents include, without limitation, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, sphingoglycolipids, fatty alcohols, fatty acids, mineral oils, and mixtures thereof. Preferably, the leachable tear stabilizing agent is a phospholipid, monoglyceride, diglyceride, triglyceride, glycolipid, glyceroglycolipid, sphingolipid, sphingoglycolipid, fatty acid containing from 8 to 36 carbon atoms, fatty alcohol containing from 8 to 36 carbon atoms ...

In the context of the present invention, the SiHy lens composition may be a solution or a melt at a temperature of from about 20 ° C to about 85 ° C. Preferably, the polymerizable composition is a solution of all necessary components in a suitable solvent or in a mixture of suitable solvents.

The SiHy lens composition can be prepared by dissolving all necessary components in any suitable solvent such as water, a mixture of water and one or more organic solvents miscible with water, in an organic solvent, or a mixture of one or more organic solvents, as is known a person skilled in the art.

Examples of preferred organic solvents include, without limitation, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g. acetone, methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, n-butyl propylene glycol ether-butyl ether tripropylene glycol, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, isopropyl lactate, methylene chloride, 2-butanol, 2-propanolonexol, exactanol pentanol, 3-pentanol, 2-g hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl alcohol, 2-methyl-2 -pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl -2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl -3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3 -octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2 -pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy -2-methyl-2-propanol 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-propanol, tert-a milic alcohol, isopropanol, 1-methyl-2-pyrrolidone, N, N-dimethylpropionamide, dimethylformamide, dimethylacetamide, dimethylpropionamide, N-methylpyrrolidinone, and mixtures thereof.

Numerous compositions for SiHy lenses are described in numerous patents and patent applications published prior to the filing date of this application. All of these can be used to make a preformed SiHy lens and in turn form the inner layer of the SiHy contact lens of the present invention if they provide a SiHy material having the Dk value and water content indicated above. SiHy lens composition for making commercial SiHy lenses such as lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A, senofilcon A, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, filcon II 3, can also be used to make preformed SiHy contact lenses (the inner layer of the SiHy contact lens of the present invention).

Molds for making contact lenses are well known to the person skilled in the art and are, for example, used in injection molding or centrifugal casting. For example, a mold (for injection molding) typically contains at least two sections (or portions) or mold halves, i. E. the first and second halves of the forms. The first mold half forms the first mold (or optical) surface and the second mold half forms the second mold (or optical) surface. The first and second mold halves are arranged to be connected to each other so that a lens-forming cavity is formed between the first forming surface and the second forming surface. The mold half forming surface is the cavity forming surface of the mold and is in direct contact with the lens forming material.

Methods for making mold sections for contact lens injection molding are generally well known to those of ordinary skill in the art. The method of the present invention is not limited to any particular mold making technology. In fact, any mold making technique can be used in the present invention. The first and second mold halves can be manufactured using various technologies such as injection molding or turning on a lathe. Examples of suitable techniques for making mold halves are disclosed in U.S. patents. No. 4444711 issued by Schad; 4,460,534 issued by Boehm et al .; 5,843,346 issued by Morrill; and 5894002 issued by Boneberger et al., which are also included in the present invention by reference.

For the manufacture of molds for the production of contact lenses, you can use almost all materials used in the art for the manufacture of molds. For example, a polymeric material such as polyethylene, polypropylene, polystyrene, PMMA, Topas ^® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene, commercially available from Ticona GmbH of Frankfurt, Germany and Summit , New Jersey) , and the like ... You can use other materials that transmit UV radiation, such as quartz glass and sapphire.

In a preferred embodiment, reusable forms are used and the silicone hydrogel lens composition is actinically cured with spatially confined actinic radiation to form a SiHy contact lens. Examples of preferred reusable forms are those disclosed in U.S. Patent Application Nos. 08/274942 filed July 14, 1994, 10/732566 filed December 10, 2003, 10/721913 filed November 25, 2003, and US No. 6,627,124, which in their entirety are incorporated into the present invention by reference. Forms reusable can be made from quartz, glass, sapphire, CaF _2, from the cyclic olefin copolymer (such as for example, Topas ^® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene) manufactured by Ticona GmbH of Frankfurt, Germany, and Summit, New Jersey, Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY), polymethyl methacrylate (PMMA), polyoxymethylene from DuPont (Delrin), Ultem® (polyetherimide) from GE Plastics, PrimoSpire ®, etc.

In the context of the present invention, the silicone hydrogel (bulk material) of the inner layer has an oxygen permeability of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90 barrers, most preferably at least about 110 bbl. The silicone hydrogel material may also have a (first) WC _SiHy water content of about 10% to about 70%, preferably about 10% to about 65%, more preferably about 10% to about 60%; even more preferably from about 15% to about 55%, most preferably from about 15% to about 50 wt. %. The silicone hydrogel material may also have a bulk modulus or bulk Young's modulus (below, the terms "softness", "modulus" and "Young's modulus" are used interchangeably herein to refer to bulk modulus, unless the word "surface" is added to the term. ") equal to about 0.3 MPa to about 1.8 MPa, preferably from 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa. The oxygen permeability, elastic modulus and water content of the inner layer of the silicon hydrogel material SiHy of the contact lens of the present invention can be determined by measuring the oxygen permeability, elastic modulus, and water content of the preformed SiHy lens from which the inner layer is formed. It should be understood that, as a reasonable approximation, the modulus of elasticity of the SiHy contact lens of the present invention can be considered the modulus of elasticity of the silicone hydrogel material of the inner layer due to the much thinner outer hydrogel layers. The person skilled in the art is well aware of how to determine the modulus and water content of a silicone hydrogel material or SiHy contact lens. For example, for all commercially available SiHy contact lenses, elastic modulus and water content are reported.

The two outer hydrogel layers of a SiHy contact lens of the present invention are preferably substantially identical and are a crosslinked coating applied to a preformed SiHy contact lens having the desired Dk, water content and bulk modulus.

The layered structural configuration of the SiHy contact lens of the present invention can be determined by atomic force microscopy (AFM) analysis of the SiHy section of the contact lens in a fully hydrated state (i.e. directly in water or in buffered saline) as described above and shown in the examples. Surface moduli of a section can be characterized (visualized) using AFM (for example, force-volume mode) to visualize any changes in modulus of the surface from the surface of the rear side to the surface of the front side of the section. A significant change (for example, about 20% or more, preferably about 30% or more) observed for the surface modulus (by examining an AFM image) in a thickness of about 0.04 μm, preferably about 0.03 μm, more preferably about 0.02 µm, even more preferably about 0.01 µm along the shortest line between the outer and inner surfaces of the cross-sectional SiHy contact lens in a fully hydrated state indicates a transition from one layer to another layer. The average thickness of each outer hydrogel layer can be determined from the AFM image, as is well known to a person skilled in the art.

The two outer hydrogel layers of the SiHy contact lens of the present invention have a substantially constant thickness. They combine at the outer edge of the contact lens and completely cover the inner layer of the silicone hydrogel material. The thickness of each outer hydrogel layer is from about 0.1 microns to about 20 microns, preferably from about 0.25 microns to about 15 microns, even more preferably from about 0.5 microns to about 12.5 microns, most preferably from about 1 μm to about 10 μm. The thickness of the outer hydrogel layers (or crosslinked coating) of the SiHy contact lens of the present invention is determined by AFM analysis of the fully hydrated section of the SiHy contact lens as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably no more than about 30% (i.e., 30% or less), more preferably no more than about 20% (20% or less), more preferably no more than about 10% ( 10% or less) of the thickness at the center of the SiHy contact lens when fully hydrated.

It should be understood that the layered structural configuration of a SiHy contact lens of the present invention can also be quantified by scanning electron microscopy (SEM) analysis of a freeze-dried section of a SiHy contact lens as shown in the examples. SEM can detect different compositions and / or structures for each layer of a SiHy cross-section of a contact lens in a freeze-dried state. A significant change (e.g., about 20% or more, preferably about 30% or more) observed in the composition and / or significant (visually detectable) structural changes (when examining an SEM image) in a thickness of about 0, 04 µm, preferably about 0.03 µm, more preferably about 0.02 µm, even more preferably about 0.01 µm in the freeze-dried state of the SiHy contact lens indicates a transition from one layer to another. However, the thickness value based on SEM analysis of the section of the freeze-dried SiHy lens is usually less than the actual thickness due to compression of the outer hydrogel layers, the transition layer, if possible, and the inner layer after freeze-drying.

In accordance with this aspect of the present invention, the two outer hydrogel layers (front and back hydrogel layers) of the SiHy contact lens of the present invention have a (c) (second) water content, which must be greater than the (first) water content (WC _SiHy ) in the inner layer of the silicone hydrogel material, and more preferably should be at least about 1.2 times (i.e. 120%) greater than the (first) water content (WC _SiHy ) in the inner layer of the silicone hydrogel material. It is assumed that the swelling ratio in water for each outer hydrogel layer correlates with the water content in it and, in a good approximation, can characterize the water content in the outer hydrogel layer. In alternative preferred embodiments, in which the water content (WC _SiHy ) in the inner layer of the silicone hydrogel material is about 55% or less, the water swell ratio for each outer hydrogel layer is at least about 150%; if the water content (WC _SiHy ) in the inner layer of the silicone hydrogel material is about 60% or less, then the water swelling ratio for each outer hydrogel layer is at least about 200%; if the water content (WC _SiHy ) in the inner layer of the silicone hydrogel material is about 65% or less, the water swell ratio for each outer hydrogel layer is at least about 250%; if the water content (WC _SiHy ) in the inner layer of the silicone hydrogel material is about 70% or less, then the water swell ratio for each outer hydrogel layer is not less than about 300%.

It should be understood that the water content of the front and back outer hydrogel layers (crosslinked coating) can be more accurately determined by the procedures described in Example 23. Alternatively, the water content of the two outer hydrogel layers (crosslinked coating) can be determined using an article containing a non-absorbent water thin substrate and a crosslinked coating thereon, where the crosslinked coating is applied to the non-water absorbing thin substrate in a coating procedure identical to that used for a SiHy contact lens under substantially identical conditions. The water content of each hydrogel outer layer can then be determined from the difference in dry and hydrated weight of the article containing the crosslinked coating.

In the context of the present invention, each of the two outer hydrogel layers is substantially free of silicon, preferably completely free of silicon. However, it is well known that if X-ray electron spectroscopy (XES) is used to establish the presence or absence of silicon in the outer hydrogel layer (usually the probing depth is from 1.5 to 6 nm), the samples inevitably become contaminated with silicon from the environment, as evidenced by detection with XPS silicon on the surface of samples that theoretically do not contain silicon atoms, such as, for example, polyethylene sheet, contact lens DAILIES® AquaComfortPlus ™, available from CIBA VISION Corporation, or ACUVUE® Moist, manufactured by Johnson & Johnson (see example below 21). The term "substantially free of silicon" is used in this application to indicate that the atomic percent content of silicon on the surface, as measured by XPS on a SiHy contact lens, is less than about 200%, preferably less than about 175%, more preferably less about 150%, even more preferably less than about 125 atomic. % silicon, based on control, known to be inherently (theoretically) free of silicon (e.g. polyethylene sheet, DAILIES® AquaComfortPlus ™ contact lens manufactured by CIBA VISION Corporation, or ACUVUE® Moist manufactured by by Johnson & Johnson). Alternatively, each SiHy outer hydrogel layer of a contact lens of the present invention is substantially free of silicon, as evidenced by atomic percent silicon content of about 5% or less, preferably about 4% or less, even more preferably about 3 % or less, based on the content of all elements, determined by analysis by means of RES of a contact lens in a dried state. It should be understood that a small amount of silicon can optionally be included (but preferably if not included) in the polymer network of the outer hydrogel layer so that it does not significantly degrade the surface characteristics (hydrophilicity, wettability, and / or surface smoothness) of the SiHy contact lens.

In a preferred embodiment, the front and back hydrogel layers (crosslinked coating) have a crosslinking density (or crosslinking density) sufficient to form a crosslinked coating or outer hydrogel layers (i.e., a SiHy contact lens) that are highly resistant to finger rubbing, about which indicates the absence of cracking lines on the surface, visible in a dark field after rubbing the SiHy contact lens with your fingers. It is believed that surface cracking caused by rubbing with fingers may reduce the smoothness of the surface and / or may not be able to prevent the migration of silicon to the surface (impact). Surface cracking can also indicate excessive crosslink density in the surface layers, which can affect the modulus of elasticity of the surface. Preferably, the non-silicone hydrogel material in the outer hydrogel layers (crosslinked coating) contains crosslinks formed from azetidinium groups by a thermally initiated coupling reaction.

In another preferred embodiment, the front and rear surfaces have a low surface concentration of negatively charged groups, including carboxy groups, characterized by adhesion of no more than about 200, preferably no more than about 160, more preferably no more than about 120, even more preferably no more than about 90, most preferably no more than about 60 positively charged particles when studying the adhesion of positively charged particles. A minimum surface concentration of negatively charged groups (e.g. carboxy groups) on a SiHy contact lens of the present invention is desirable, since contact lenses having a high surface concentration of negatively charged groups (e.g. carboxy groups) are susceptible to strong dirt adhesion when handled by the patient, strong protein adhesion during wearing (it is assumed that most of the proteins in the lacrimal fluid are positively charged), significant deposition and accumulation of antimicrobial agents such as polyhexamethylene biguanide (PHMB) contained in contact lens care solutions. In order to have a low surface concentration of negatively charged groups (eg carboxy groups), the front and back hydrogel layers must have a relatively low carboxylic acid content. Preferably, if the front and back hydrogel layers have a carboxylic acid content of about 20 wt. % or less, preferably about 15 wt. % or less, even more preferably about 10 wt. % or less, most preferably about 5 wt. % or less.

In another preferred embodiment, the SiHy contact lens of the present invention exhibits good surface smoothness with a critical coefficient of friction (referred to as CCF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, the SiHy contact lens of the present invention preferably has a surface smoothness better than ACUVUE OASYS or ACUVUE TruEye when blinded using the surface smoothness techniques described in Example 1.

In another preferred embodiment, the SiHy contact lens of the present invention also comprises, in its layered structural configuration, two transition layers of polymer material (s), schematically shown in FIG. 2. Each of the two transition layers 115 is located between the inner layer 110 and one of the two outer hydrogel layers 120. Each transition layer has a substantially constant thickness. The thickness of each transition layer is not less than about 0.05 microns, preferably from about 0.05 microns to about 10 microns, more preferably from about 0.1 microns to about 7.5 microns, even more preferably from about 0.15 microns to about 5 microns. The transition layers merge at the outer edge of the contact lens and completely cover the inner layer of the silicone hydrogel material. The presence and thickness of the transition layers can preferably be determined by AFM analysis of the SiHy section of the contact lens in a fully hydrated state, as described above for the outer hydrogel layers and inner layers.

These two SiHy transition layers of the contact lens of the present invention are essentially a base (or primer) coat that is applied to a preformed SiHy contact lens having the required Dk, water content and bulk modulus, prior to application of the crosslinked coating (outer hydrogel layers). Transition layers (basecoat) are designed to anchor / attach the outer hydrogel layers. Preferably, the transition layers comprise a carboxy-containing (COOH) polymer, preferably a homo- or copolymer of acrylic acid or methacrylic acid or C ₂ -C ₁₂ alkyl acrylic acid. It should be understood that the carboxy-containing polymer can penetrate the bulk material and exit into the outer hydrogel layers. If such penetration into the inner layer of the silicone hydrogel material occurs, each transition layer will contain a carboxy-containing polymer and a silicone hydrogel, which are intertwined with each other. It is also believed that the presence of transition layers, especially if they contain a polymer containing carboxy groups, can lead to a relatively high water content in the thicker layer and / or to the formation of a reservoir of water in the outer hydrogel layers due to the good ability of carboxy groups to bind water. In addition, even if the transition layer may have a high content of carboxy groups, it will have a minimal adverse effect on the surface concentration of carboxy groups SiHy of the contact lens, since the surface concentration of carboxy groups is mainly determined by the outer hydrogel layers that completely cover the transition layer. Outer hydrogel layers, which have a low surface concentration of carboxy groups, can prevent the deposition of positively charged proteins from the tear fluid of a patient wearing a lens.

In another preferred embodiment, the front and back hydrogel layers independently have a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%. most preferably at least about 40%, relative to the inner layer.

The front and back hydrogel layers are preferably formed from the same or substantially the same materials (preferably no silicon at all) and can be formed by applying and crosslinking a water-soluble and thermally crosslinkable hydrophilic polymer material onto a preformed SiHy contact lens that contains amino groups and / or a carboxy group on the surface of a contact lens and / or near it, or a basecoat containing amino groups and / or carboxy groups, where the preformed SiHy contact lens after crosslinking forms an inner layer.

In the context of the present invention, a preformed SiHy contact lens may itself contain amino groups and / or carboxy groups, or be modified to include them on or near its surface.

If the preformed SiHy contact lens itself contains amino and / or carboxy groups on or near its surface, it is made by polymerizing a silicone hydrogel lens composition containing a reactive vinyl monomer.

Examples of preferred reactive vinyl monomers include, but are not limited to, amino-C ₂ -C ₆ alkyl (meth) acrylate, C ₁ -C ₆ alkylamino-C ₂ -C ₆ alkyl (meth) acrylate, allylamine, vinyl amine, amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₁₂ -alkyl acrylic acid (e.g. methacrylic acid, ethyl acrylic acid , propyl acrylic acid, butyl acrylic acid, pentyl acrylic acid, etc.), N, N-2-acrylamidoglycolic acid, beta-methyl acrylic acid (crotonic acid), alpha-phenylacrylic acid, beta-acryloxypropionic acid, sorbic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesoconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. Preferably, the SiHy contact lens is made from a lens composition containing at least one reactive vinyl monomer selected from the group consisting of amino-C ₂ -C ₆ -alkyl (meth) acrylate, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₁ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid , C ₁ -C ₁₂ -alkyl acrylic acid, N, N-2-acrylamidoglycolic acid, and combinations thereof.

The lens composition preferably contains 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 wt. % of the reactive vinyl monomer described above.

The preformed SiHy contact lens can also be surface treated to form a reactive base coat containing amino and / or carboxy groups on the surface of the contact lens. Examples of surface treatment techniques include, but are not limited to, surface treatment with an energy source (e.g., plasma, static electricity, radiation, or other energy source), chemical treatment, chemical vapor deposition, grafting hydrophilic vinyl monomers or macromers to the surface of an article, layer-by-layer coating ("PSL coating"), carried out according to the methods described in US patents Nos. 6451871, 6719929, 6793973, 6811805, and 6S96926 and U.S. Patent Application Publications. No. 2007/0229758 A1, 2008/0152800 A1, and 2008/0226922 A1, (which are incorporated by reference in their entirety into the present invention). "PSL coating" as used in the present invention means a coating that is not covalently bound to the polymer matrix of a contact lens and which is obtained by layer-by-layer ("PSL) deposition of charged or chargeable (by protonation or deprotonation) and / or uncharged materials onto the lens. PSL coating can consist of one or more layers.

Preferably, if the surface treatment is the formation of a PSL coating. In this preferred embodiment (i.e., an embodiment of a reactive PSL basecoat), the resulting silicone hydrogel contact lens comprises a reactive PSL basecoat comprising at least one reactive polymer layer (i.e., a polymer containing pendant amino groups and / or carboxy groups), where the reactive PSL basecoat is obtained by reacting a contact lens with a reactive polymer solution. The contact lens may interact with the coating solution of the reactive polymer by immersing it in the coating solution or by spraying it with the coating solution. One interaction technique involves only immersing the contact lens in a bath of coating solution for a period of time, or alternatively, dipping the contact lens sequentially into several baths of coating solution for a specified shorter period of time for each bath. Another interaction technique involves only spraying with a coating solution. However, a variety of alternatives include various combinations of spraying and immersion steps that can be devised by one of ordinary skill in the art. The duration of contact of the contact lens with the reactive polymer coating solution can be 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.

In this embodiment d of the reactive PSL basecoat, the reactive polymer may be a linear or branched polymer containing pendant amino and / or carboxy groups. Any polymers containing pendant amino and / or carboxy groups can be used as a reactive polymer to form basecoats on silicone hydrogel contact lenses. Examples of such reactive polymers include, but are not limited to: a homopolymer of a reactive vinyl monomer; copolymer of two or more reactive vinyl monomers; a copolymer of a reactive vinyl monomer with one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers that do not contain any carboxy or (primary or secondary) amino group); polyethyleneimine (PEI); polyvinyl alcohol containing side amino groups; carboxy-containing cellulose (eg, carboxymethyl cellulose, carboxyethyl cellulose, carboxypropyl cellulose); hyaluronate; chondroitin sulfate; poly (glutamic acid); poly (aspartic acid); and combinations thereof.

Any of the preferred reactive vinyl monomers described above can be used in this embodiment to form a reactive polymer for forming a reactive PSL basecoat.

Preferred examples of non-reactive hydrophilic vinyl monomers not containing a carboxy or amino group include, but are not limited to, acrylamide (AAM), N, N-dimethylacrylamide (DMA) methacrylamide, N, N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NV , -dimethylaminoethyl methacrylate (DMAEM), N, N-dimethylaminoethyl acrylate (DMAEA), N, N-dimethylaminopropyl methacrylamide (DMAPMAA), N, N-dimethylaminopropyl acrylamide (DMAPA), propylene methacrylamide, N-acrylamide [tris (hydroxymethyl) methyl] -acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl- 5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methyl-2-pyrrolidone, 2-hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, C ₁ -C ₄ -alkoxypolyethylene glycol (meth) acrylate with a weight average molecular weight of up to 1500 Da, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl new alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer), phosphorylcholine-containing vinyl monomer (including (meth) acryloyloxyethylphosphorylcholine and described in US Pat. No. 5,461,433, which is incorporated herein by reference in its entirety), and combinations thereof.

Preferably, the reactive polymers to form a reactive PSL basecoat include polyacrylic acid, polymethacrylic acid, poly (C ₂ -C ₁₂ alkyl acrylic acid), acrylic acid methacrylic acid copolymer, poly (N, N-2-acrylamidoglycolic acid ), copolymer of acrylic acid with acrylamide, copolymer of acrylic acid with vinyl pyrrolidone, copolymer of C ₂ -C ₁₂ -alkyl acrylic acid with acrylamide, copolymer of C ₂ -C ₁₂ -alkyl acrylic acid with vinyl pyrrolidone, hydrolyzed copolymer of (meth) acrylic acid with hydrolized vinyl C ₂ -C ₁₂ -alkyl acrylic acid with vinyl acetate, polyethyleneimine (PEI), homo- or copolymer of polyallylamine hydrochloride (PAG), homo- or copolymer of polyvinylamine, or combinations thereof.

The weight average molecular weight M _{w of the} reactive polymer for forming the reactive PSL basecoat is at least about 10,000 Da, preferably at least about 50,000 Da, more preferably from about 100,000 Da to 5,000,000 Da.

A reactive polymer solution for forming a reactive PSL basecoat on contact lenses can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive polymer is dissolved in a mixture of water and one or more organic solvents, in an organic solvent, or in a mixture of one or more organic solvents. It is contemplated that a solvent system containing at least one organic solvent can swell the preformed SiHy contact lens so that a portion of the reactive polymer can penetrate into the preformed SiHy contact lens and increase the durability of the reactive basecoat. Any organic solvents described above can be used to prepare a reactive polymer solution as long as they can dissolve the reactive polymer.

In another preferred embodiment, the preformed SiHy contact lens inherently contains amino groups and / or carboxy groups at or near its surface and its surface is further processed to form a reactive PSL basecoat containing amino groups and / or carboxy groups.

In another preferred embodiment (reactive plasma basecoat), the preformed SiHy contact lens is plasma treated to form a covalently bonded reactive plasma basecoat on the contact lens, i. E. one or more reactive vinyl monomers (any of those described above) are polymerized by exposure to an electric discharge plasma (so-called plasma-induced polymerization). The term "plasma" means an ionized gas, for example, formed by a glow discharge, which can be composed of electrons, ions of any charge, atoms and molecules in the ground or any higher state of any form of excitation, as well as photons. It is often referred to as "low temperature plasma". For an overview of plasma polymerization and its applications, see R. Hartmann "Plasma polymerisation: Grundlagen, Technik und Anwendung, Jahrb. Oberflachentechnik (1993) 49, pp. 283-296, Battelle-Inst. EV Frankfurt / Main Germany; H. Yasuda, "Glow Discharge Polymerization", Journal of Polymer Science: Macromolecular Reviews, vol 16 (1981), pp. 199-293; H. Yasuda, "Plasma Polymerization", Academic Press, Inc. (1985); Frank Jansen, "Plasma Deposition Processes", in "Plasma Deposited Thin Films", ed. By T. Mort and F. Jansen, CRC Press Boca Raton (19); O. Auciello et al. (Ed.) "Plasma-Surface Interactions and Processing of Materials "publ. by Kluwer Academic Publishers in NATO ASI Series; Series E: Applied Sciences, vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali" Plasma Polymerization of Selected Organic Compounds ", Polymer, vol. 37 (1996) pp. 333-341. It is preferred if the plasma-induced polymerization is a plasma-induced polymerization "after luminescence "described in WO 98028026 (which is incorporated herein by reference in its entirety). For plasma-induced "afterglow" polymerization, the surface of the contact lens is first treated with a non-polymerizable plasma-forming gas (e.g. H2, He or Ar) and then, in the next step, the surface thus activated is treated with a vinyl monomer containing an amino or carboxy group (any reactive vinyl monomer, described above), with the cessation of plasma exposure. Activation leads to plasma-induced formation of radicals on the surface, which at the next stage initiate the polymerization of the vinyl monomer on it.

In the context of the present invention, the water-soluble and thermally crosslinkable hydrophilic polymeric material for forming the outer hydrogel layers (or crosslinked coating) contains crosslinkable groups, preferably thermally crosslinkable groups, more preferably azetidinium groups. Preferably, the water-soluble and thermally crosslinkable hydrophilic polymer material to form the outer hydrogel layers (or crosslinked coating) is a partially crosslinked polymer material that contains a three-dimensional network and crosslinkable (preferably thermally crosslinkable) groups, more preferably azetidinium groups in the network ... The term "partially crosslinked" in relation to a polymeric material means that the crosslinking groups of the starting materials intended for obtaining the polymeric material by the crosslinking reaction are not completely consumed. Examples of crosslinkable groups include, without limitation, azetidinium groups, epoxy groups, isocyanate groups, aziridine groups, azlactone groups, and combinations thereof.

In a preferred embodiment, the water-soluble and thermally crosslinkable hydrophilic polymeric material for forming the outer hydrogel layers (or crosslinked coating) contains (i) from about 20% to about 95 wt. % of the first polymer chains formed from an epichlorohydrin functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80 wt. % hydrophilic moieties or second polymer chains formed from at least one hydrophilicity enhancing agent containing at least one reactive functional group selected from the group consisting of an amino group, a carboxy group, a thio group, and a combination thereof, wherein the hydrophilic moieties or second polymer chains are covalently linked with the first polymer chains using one or more covalent bonds, each of which is formed between one azetidinium group of an epichlorohydrin functionalized polyamine or polyamidoamine and one amino, carboxy or thio group of the hydrophilicity enhancing agent, and (iii) azetidinium groups that are part of the first polymer chains or side or end groups covalently linked to the first polymer chains.

With such a water-soluble and thermally crosslinkable hydrophilic polymer material, the outer hydrogel layers (or crosslinked coating) can be formed by conventional heating of a preformed SiHy contact lens (containing amino and / or carboxy groups on the surface of the contact lens and / or near it or base coating containing amino and / or carboxy groups) in aqueous solution in the presence of a hydrophilic polymer material and at a temperature of from about 40 ° C to about 140 ° C for a period of time sufficient to covalently bond the hydrophilic polymer material to the surface of a contact lens by covalent bonds , each of which is formed between one azetidinium group of the hydrophilic polymeric material and one of the amino groups and / or carboxy groups located on the surface of the contact lens and / or near it, and thus form a hydrophilic coating on the contact lens. It should be understood that any water-soluble and thermally crosslinkable hydrophilic polymer material containing crosslinkable groups (eg, as described above) can be used in the present invention to form the anterior and posterior outer hydrogel layers of a SiHy contact lens.

In the context of the present invention, the water-soluble and thermally crosslinkable hydrophilic polymeric material containing azetidinium groups comprises (i.e., has a composition comprising) from about 20% to about 95%, preferably from about 35% to about 90%, more preferably from about 50% to about 85 wt. % of the first polymer chains formed 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 wt. % hydrophilic moieties or second polymer chains formed from at least one hydrophilicity enhancing agent containing at least one reactive functional group selected from the group consisting of an amino group, a carboxy group, a thio group, and a combination thereof. The composition of the hydrophilic polymer material is determined by the composition (based on the total weight of the reactants) of the reactant mixture used to obtain the thermally crosslinkable hydrophilic polymer material by the crosslinking reactions shown in Scheme I above. For example, if the reactant mixture contains about 75 wt. % functionalized with epichlorohydrin polyamine or polyamidoamine and about 25 wt. % of at least one increasing hydrophilicity agent based on the total weight of the reactants, the resulting hydrophilic polymer material contains about 75 wt. % of the first polymer chains formed from functionalized with epichlorohydrin polyamine or polyamidoamine, and about 25 wt. % hydrophilic moieties or second polymer chains formed from said at least one hydrophilicity enhancing agent. The azetidinium groups of the thermally crosslinkable hydrophilic polymeric material are those azetidinium groups (epichlorohydrin functionalized polyamine or polyamidoamine) that do not participate in crosslinking reactions to produce the thermally crosslinkable hydrophilic polymeric material.

An epichlorohydrin-functionalized polyamine or polyamidoamine can be prepared by reacting epichlorohydrin with a polyamine or polymer containing primary or secondary amino groups. For example, poly (alkyleneimines) or poly (amidoamine), which is a condensation product formed from a polyamine and a dicarboxylic acid (eg, adipic acid-diethylenetriamine copolymers), can react with epichlorohydrin to form an epichlorohydrin functionalized polymer. Similarly, a homopolymer or copolymer of aminoalkyl (meth) acrylate, monoalkylaminoalkyl (meth) acrylate, aminoalkyl (meth) acrylamide, or monoalkylaminoalkyl (meth) acrylamide can also react with epichlorohydrin to form an epichlorohydrin functionalized polyamine. The reaction conditions for the functionalization of polyamine or polyamidoamine with epichlorohydrin are described in EP 1465931 (which is incorporated herein by reference in its entirety). A preferred polymer is a functionalized epichlorohydrin with polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), such as, for example, Kymene® resin or Polycup ^® (epichlorohydrin-functionalized copolymers of adipic acid-diethylenetriamine), marketed by Hercules Polycup or ^® or Servamine ^® resins available from Servo / Delden.

Any suitable hydrophilicity increasing agents can be used in the present invention as long as they contain at least one amino group, at least one carboxy group and / or at least one thio group.

A preferred class of hydrophilicity enhancing agents includes, without limitation: amino, carboxy, or thio group-containing monosaccharides (e.g., 3-amino-1,2-propanediol, 1-thioglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosamic acid, mannosamine, 1,4-lactone of sugar acid, saccharic acid, ketodeoxynonulosonic acid, N-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino 1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethylgluconamide); disaccharides containing amino, carboxy or thio groups (for example, sodium salt of chondroitindisaccharide, di (β-D-xylopyranosyl) amine, digalacturonic acid, heparine disaccharide, hyaluronic acid disaccharide, lactobionic acid); and oligosaccharides containing amino, carboxy or thio groups (eg sodium carboxymethyl-β-cyclodextrin, trigalacturonic acid); and combinations thereof.

Another preferred class of hydrophilic enhancing agents includes hydrophilic polymers containing one or more amino groups, carboxy groups, and / or thio groups. More preferably, the content of monomer units containing amino group (-NHR ', where R' is as defined above), carboxy group (-COOH) and / or thio group (-SH) in the hydrophilic polymer as increasing the hydrophilicity agent is less than about 40%, preferably less than about 30%, more preferably less than about 20%, even more preferably less than about 10 wt. % based on the total weight of the hydrophilic polymer.

One preferred class of hydrophilic polymers as hydrophilic enhancing agents includes polysaccharides containing amino or carboxy groups, such as, for example, carboxymethyl cellulose (with a carboxy group content of about 40% or less, as determined based on the composition of the repeating units,

- [C ₆ H _10-m O ₅ (CH ₂ CO ₂ H) _m ] -, where t is 1 to 3), carboxyethyl cellulose (with a carboxy group content of about 36% or less based on the composition of the repeating units ,

- [C ₆ H _10-m O ₅ (C ₂ H ₄ CO ₂ H) _m ] -, where m is from 1 to 3) carboxypropyl cellulose (with a carboxy group content of about 32% or less, based on the composition of the repeating links,

- [C ₆ H _10-m O ₅ (C ₃ H ₆ CO ₂ H) _m ] -, where m is from 1 to 3), hyaluronic acid (with a carboxy group content of about 11%, which is based on the composition of the repeating units, - (C ₁₃ H ₂₀ O ₉ NCO ₂ H) -), chondroitin sulfate (with a carboxy group content of about 9.8%, which is based on the composition of the repeating units,

- (C ₁₂ H ₁₈ O ₁₃ NS CO ₂ H) -) or combinations thereof.

Another preferred class of hydrophilic polymers for use as hydrophilic enhancing agents includes, without limitation: poly (ethylene glycol) (PEG) containing one amino, carboxy, or thio group (eg, PEG-NH ₂ , PEG-SH, PEG-COOH); H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG-COOH; HOOC-PEG-SH; H ₂ N-PEG-SH; multi-arm PEG containing one or more amino groups, carboxy groups, or thio groups; PEG dendrimers containing one or more amino groups, carboxy groups, or thio groups; containing 2 terminal amino groups or 2 terminal carboxy groups of a homo- or copolymer of a non-reactive hydrophilic vinyl monomer; containing an amino terminal group or a terminal carboxy group of a homo- or copolymer of a non-reactive hydrophilic vinyl monomer; copolymer, which is the product of polymerization of the composition containing (1) about 60 wt. % 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 wt. % of one or more reactive vinyl monomers and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least one phosphorylcholine-containing vinyl monomer; and combinations thereof. Reactive vinyl monomer (s) and non-reactive hydrophilic vinyl monomer (s) are as described above.

More preferably, the hydrophilic polymer used as the hydrophilicity enhancing agent is PEG-NH ₂ ; PEG-SH; PEG-COOH; H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG-COOH; HOOC-PEG-SH; H ₂ N-PEG-SH; multi-arm PEG containing one or more amino groups, carboxy groups, or thio groups; PEG dendrimers containing one or more amino groups, carboxy groups, or thio groups; monoamino, monocarboxy, diamino, or dicarboxy terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide (AAM), N, N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinylpyrrolidone (NVP), N-vinylpyrrolidone (NVP) -N-methylacetamide, glycerol (meth) acrylate, hydroxyethyl (meth) acrylate, N-hydroxyethyl (meth) acrylamide, C ₁ -C ₄ -alkoksipolietilenglikol (meth) acrylate having a weight average molecular weight equal 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 (meth) acrylamide, (meth) acryloyloxyethylphosphorylcholine, and combinations thereof; copolymer, which is the product of polymerization of the composition containing (1) from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15 wt. % (meth) acrylic acid, C ₂ -C ₁₂ -alkyl acrylic acid, vinylamine, allylamine, and / or amino-C ₂ -C ₄ -alkyl (meth) acrylate, and (2) (meth) acryloyloxyethylphosphorylcholine and / or at least at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide, N, N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth) acrylate, hydroxyethyl (meth) acrylate, N-hydroxyethyl acrylamide, C ₁ -C ₄ -alkoxypolyethylene glycol (meth) acrylate having a weight average molecular weight of up to 400 Da, vinyl alcohol and their combination.

Most preferably, the hydrophilic enhancing agent as the hydrophilic enhancing agent is PEG-NH ₂ ; PEG-SH; PEG-COOH; monoamino, monocarboxy, diamino or dicarboxy terminated polyvinylpyrrolidone; monoamino, monocarboxy, diamino or dicarboxy terminated polyacrylamide; monoamino, monocarboxy, diamino or dicarboxy terminated with poly (DMA); monoamino or monocarboxy, diamino or dicarboxy terminated copolymer of DMA with NVP; monoamino, monocarboxy, diamino or dicarboxy terminated copolymer NVP with N, N-dimethylaminoethyl (meth) acrylate; monoamino, monocarboxy, diamino or dicarboxy terminated poly (vinyl alcohol); monoamino, monocarboxy, diamino or dicarboxy terminated poly [(meth) acryloyloxyethylfossphorylcholine] homopolymer or copolymer; monoamino, monocarboxy, diamino or dicarboxy terminated NVP vinyl alcohol copolymer; monoamino, monocarboxy, diamino or dicarboxy terminated copolymer of DMA with vinyl alcohol; copolymer of acrylic acid with acrylamide containing from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15 wt. % (meth) acrylic acid; copolymer of (meth) acrylic acid with NVP containing from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15 wt. % (meth) acrylic acid; copolymer, which is the product of polymerization of a composition containing (1) (meth) acryloyloxyethylphosphorylcholine 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 wt. % carboxylic acid containing vinyl monomer and / or containing an amino group vinyl monomer and a combination thereof.

Functionalized PEGs and functionalized multi-arm PEGs are available from various commercial suppliers such as Polyscience and Shearwater Polymers, inc. etc.

Monoamino, monocarboxy, diamino, or dicarboxy terminated homo- or copolymers of one or more non-reactive hydrophilic vinyl monomers or phosphorylcholine-containing vinyl monomer can be prepared by the procedures described in U.S. Patent No. No. 6218508, which in its entirety is included in the present invention by reference. For example, to prepare a 2-terminal amino or 2-terminal carboxylic acid homo- or copolymer of a non-reactive hydrophilic vinyl monomer, a non-reactive vinyl monomer, a chain transfer agent containing an amino or carboxy group (e.g. acid or other hydroxymercaptans, aminomercaptans or carboxy-containing mercaptans) and optionally another vinyl monomer are copolymerized (thermally or actinically) with a reactive vinyl monomer (containing an amino or carboxy group) in the presence of a free radical initiator. Typically, the ratio of moles of chain transfer agent to moles of all non-reactive vinyl monomer vinyl monomers is from about 1: 5 to about 1: 100, and the ratio of moles of chain transfer agent to moles of reactive vinyl monomer is 1: 1. In this preparation, a chain transfer agent containing an amino group or a carboxy group is used to control the molecular weight of the resulting hydrophilic polymer and end the resulting hydrophilic polymer to form a hydrophilic polymer containing one terminal amino group or carboxy group, and the reactive vinyl monomer forms another terminal carboxy group or the resulting hydrophilic polymer. Likewise, a chain transfer reagent containing an amino or carboxy group (e.g., 2-aminoethanethanethiol, thiropyloic acid or other hydroxymercaptans, aminomercaptans or carboxy-containing mercaptans) and optionally other vinyl monomers are copolymerized (thermally or actinically) in the absence of any reactive vinyl monomer.

As used herein, a copolymer of a non-reactive hydrophilic vinyl monomer means the polymerization product of a non-reactive hydrophilic vinyl monomer with one or more additional vinyl monomers. Copolymers containing a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (eg, a carboxy-containing vinyl monomer) can be prepared by any well known radical polymerization technique or obtained from commercial suppliers. Copolymers containing methacryloyloxyethylphosphorylcholine and a vinyl monomer containing carboxy groups are available from NOP Corporation (eg LIPIDURE® -A and -AF).

The weight average molecular weight M _{w of a} hydrophilic polymer containing at least one amino, carboxy or thio group (as a hydrophilic enhancing agent) is preferably from about 500 to about 1,000,000, more preferably from about 1,000 to about 500,000.

In the context of the present invention, the reaction between the hydrophilicity enhancing agent and the epichlorohydrin functionalized polyamine or polyamidoamine is carried out at a temperature of from about 40 ° C to about 100 ° C, for a period of time sufficient (from about 0.3 hours 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.

In the context of the present invention, the concentration of the hydrophilicity enhancing agent relative to the concentration of the epichlorohydrin functionalized polyamine or polyamidoamine must be selected so as not to render the resulting hydrophilic polymeric material insoluble in water (i.e., having a solubility of less than 0.005 g per 100 ml of water at room temperature ), and not 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.

In the context of the present invention, heating is preferably carried out by autoclaving a preformed SiHy contact lens that contains amino groups and / or carboxy groups on the surface of the contact lens and / or near it, or a basecoat containing amino groups and / or carboxy groups, and immersed in the packaging a solution (ie, a buffered aqueous solution) containing a water-soluble thermally crosslinkable hydrophilic polymer material in a sealed lens packaging at a temperature of about 118 ° C to about 125 ° C for about 20-90 minutes. In this embodiment of the present invention, the packaging is a buffered aqueous solution that is ophthalmologically safe after autoclaving. Alternatively, preferably carried out by autoclaving a preformed SiHy contact lens that contains a basecoat and a layer of water-soluble thermally crosslinkable hydrophilic polymer material on the basecoat immersed in a packaging solution (i.e. buffered aqueous solution) in a sealed lens package at a temperature of from about 118 ° C to about 125 ° C for about 20-90 minutes.

Lens packs (or containers) are well known to the person skilled in the art for autoclaving and storage of a soft contact lens. Any lens packaging can be used in the context of the present invention. Preferably, the lens packaging is a blister pack that contains a base and a cover that is detachably attached to the base, and the base comprises a cavity for receiving a sterile packaging solution and a contact lens.

Lenses are individually wrapped, sealed, and sterilized (for example, in an autoclave at about 120 ° C or higher for at least 30 minutes)) prior to shipment to consumers. One of ordinary skill in the art should understand how to seal and sterilize lens packaging.

In the context of the present invention, the 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 thickeners) (eg, cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

The packaging solution contains a buffering agent in an amount sufficient to maintain the pH of the packaging solution within the desired range, eg, preferably within a physiologically acceptable range of about 6 to about 8.5. Any known physiologically compatible buffering agents can be used. A buffering agent suitable for use as a component of the contact lens storage composition of the present invention is known to the person skilled in the art. Examples are boric acid, borates, for example sodium borate, citric acid, citrates, for example potassium citrate, bicarbonates, for example sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris ( Bis- (2-hydroxyethyl) -imino-tris- (hydroxymethyl) -methane), bis-aminopolyols, triethanolamine, ACES (N- (2-hydroxyethyl) -2-aminoethanesulfonic acid), BES (N, N-Bis (2 -hydroxyethyl) -2-aminoethanesulfonic acid), HEPES (4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid), MES (2- (N-morpholino) ethanesulfonic acid), MOPS (3- [N-morpholino] -propanesulfonic acid), PIPES (piperazine-N, N'-bis (2-ethanesulfonic acid), TES (N- [tris (hydroxymethyl) methyl] -2-aminoethanesulfonic acid), their salts, phosphate buffers, for example, Na ₂ HPO ₄ , NaH ₂ PO ₄ and KH ₂ PO ₄ or mixtures thereof The preferred bis-aminopolyol is 1,3-bis (tris [hydroxymethyl] methylamino) propane (bis-TRIS propane) The amount of each buffering agent in the packaging solution is preferably from 0.001% to 2%, preferably 0.01% to 1%; most preferably from about 0.05% to about 0.30 wt. %.

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

The packaging solution of the present invention has a viscosity of about 1 cps to about 20 cps, preferably about 1.2 cps to about 10 cps, more preferably about 1.5 cps to about 5 cps, at 25 ° C. ...

In a preferred embodiment, the packaging solution contains 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 wt. % water-soluble thermally crosslinkable hydrophobic polymeric material of the present invention.

The packaging solution of the present invention may contain a viscosity-increasing polymer. The viscosity-increasing polymer is preferably non-ionic. The increase in the viscosity of the solution leads to the formation of a film on the lens, which can facilitate comfortable wearing of the contact lens. The viscosity-increasing component can also reduce the stress on the surface of the eye when the lens is put on, as well as reduce eye irritation.

Preferred viscosity increasing polymers include, but are not limited to, water soluble cellulose ethers (e.g., methyl cellulose (MC), ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), soluble), or mixtures thereof in water, polyvinyl alcohols (PVA), high molecular weight poly (ethylene oxide) having a molecular weight exceeding about 2000 (up to 10,000,000 Da), polyvinylpyrrolidone having a molecular weight of from about 30,000 Da to about 1,000,000 Da, copolymer of N-vinylpyrrolidone and at least at least one dialkylaminoalkyl (meth) acrylate containing 7-20 carbon atoms, and combinations thereof. Water-soluble cellulose ethers and copolymers of N-vinylpyrrolidone and dimethylaminoethyl methacrylate are the most preferred viscosity-increasing polymers. Copolymers of N-vinylpyrrolidone and dimethylaminoethyl methacrylate are commercially available, for example Copolymer 845 and Copolymer 937 from ISP.

The viscosity-increasing polymer is contained in the packaging solution in an amount ranging from about 0.01% to about 5% by weight. %, preferably from about 0.05% to about 3 wt. %, even more preferably from about 0.1% to about 1 wt. % based on the total amount of packaging solution.

The packaging solution may further comprise polyethylene glycol having a molecular weight of about 1200 or less, more preferably 600 or less, most preferably about 100 to about 500 Da.

If the crosslinked coating and / or packaging solution contains a polymeric material containing polyethylene glycol segments, the packaging solution preferably contains an α-oxo-polybasic acid or a salt thereof in an amount sufficient to provide a reduced susceptibility to oxidative degradation of the polyethylene glycol segments. A jointly owned and pending patent application (US Patent Application Publication No. 2004/0116564 A1, which is incorporated by reference in its entirety), discloses that an oxo-polybasic acid or a salt thereof can reduce oxidative stress. degradation of the PEG-containing polymeric material.

Typical α-oxo-polybasic acids or biocompatible salts thereof include, but are not limited to citric acid, 2-ketoglutaric acid, or malic acid, or biocompatible (preferably ophthalmologically compatible) salts thereof. More preferably, if the α-oxo-polybasic acid is citric or malic acid or their biocompatible (preferably ophthalmologically compatible) salts (eg sodium, potassium, etc.).

In the context of the present invention, the solution may additionally contain mucin-like substances, ophthalmologically beneficial substances and / or surfactants. The typical mucin-like substances described above, the typical ophthalmologically beneficial substances described above, the typical surfactants described above can be used in this embodiment.

In a preferred embodiment, the SiHy contact lens of the present invention has a relatively long water film disintegration time (WDP). WVDP refers to the time it takes for the water film to break (breakdown in wetting) when the underlying lens material is exposed, as determined by visual inspection. A SiHy contact lens with a longer ERVP can retain a film of water (tear fluid) on the surface for a relatively longer period of time when the lens is worn in the eye. Dry spots are less likely to form between eyelid blinks and improved wearing comfort can be provided. VDPV can be determined using the techniques described in the example below. Preferably, the SiHy contact lens of the present invention has a surface hydrophilicity with a water film disintegration time of at least about 10 seconds.

In a preferred embodiment, the SiHy contact lens of the present invention has a surface wettability of about 90 ° or less, preferably about 80 ° or less, more preferably about 70 ° or less, even more preferably about 60 ° or less, most preferably about 50 ° or less.

In a preferred embodiment, the SiHy contact lens has an oxygen permeability of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 100, most preferably at least about 120 bbl / mm.

It should be understood that while in this aspect of the present invention, various embodiments, including preferred embodiments of the present invention, may be described above separately, they can be combined and / or used together in any desired manner in the method of the present invention to form other embodiments of silicone hydrogel contact lenses of the present invention.

), где задняя наружная зона обладает средним модулем задней поверхности (обозначенным как

), где внутренняя зона обладает средним модулем внутренней поверхности (обозначенным как

), где по меньшей мере один из

и

составляет не менее примерно 20%, предпочтительно не менее примерно 25%, более предпочтительно не менее примерно 30%, еще более предпочтительно не менее примерно 35%, наиболее предпочтительно не менее примерно 40%. Предпочтительно, если передняя и задняя наружные зоны обладают толщиной, равной не менее примерно 0,1 мкм, предпочтительно от примерно 0,1 мкм до примерно 20 мкм, более предпочтительно от примерно 0,25 мкм до примерно 15 мкм, еще более предпочтительно от примерно 0,5 мкм до примерно 12,5 мкм, наиболее предпочтительно от примерно 1 мкм до примерно 10 мкм.Another aspect of the present invention is a hydrated silicone hydrogel contact lens. The hydrated silicone hydrogel contact lens of the present invention includes: a silicone hydrogel material as a bulk material, an anterior surface and an opposing posterior surface; wherein the contact lens has an oxygen permeability of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 bbl / mm, and a cross-sectional modulus profile that includes the shortest the lines between the outer and inner surfaces on the cross-sectional surface of the contact lens, the front outer zone including the front surface and the region near it, the inner zone including the center of the shortest line and the region near it, and the posterior outer zone, including the back surface and the region near it, where the anterior outer zone has a middle modulus of the anterior surface (designated as

), where the posterior outer zone has a middle modulus of the posterior surface (denoted as

), where the inner zone has an average modulus of the inner surface (denoted as

), where at least one of

and

is at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, most preferably at least about 40%. Preferably, the front and rear outer zones have a thickness of at least about 0.1 microns, preferably from about 0.1 microns to about 20 microns, more preferably from about 0.25 microns to about 15 microns, even more preferably from about 0.5 microns to about 12.5 microns, most preferably from about 1 micron to about 10 microns.

In a preferred embodiment, the hydrated silicone hydrogel contact lens may have a modulus of elasticity (or Young's modulus) of from about 0.3 MPa to about 1.8 MPa, preferably from about 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa; a water content of about 10% to about 75%, preferably about 10% to about 70%, more preferably about 15% to about 65%; even more preferably from about 20% to about 60%, most preferably from about 25% to about 55 wt. %; surface wettability having an average water contact angle of about 90 ° or less, preferably about 80 ° or less, more preferably about 70 ° or less, even more preferably about 60 ° or less, most preferably about 50 ° or less; hydrophilicity of the surface, characterized by the value of the VVP equal to not less than about 10 s; or combinations thereof.

In another preferred embodiment, the front and rear surfaces have a low surface concentration of negatively charged groups (e.g., carboxy groups) characterized by adhesion of no more than about 200, preferably no more than about 160, more preferably no more than about 120, even more preferably no more than about 90. most preferably no more than about 60 positively charged particles in a positively charged particle adhesion study. To provide a low surface concentration of negatively charged groups (eg, carboxy groups), the front and back hydrogel layers must have a relatively low carboxylic acid content. Preferably, if the front and back hydrogel layers have a carboxylic acid content of about 20 wt. % or less, preferably about 15 wt. % or less, even more preferably about 10 wt. % or less, most preferably about 5 wt. % or less.

In another preferred embodiment, the SiHy contact lens of the present invention exhibits good surface smoothness with a critical coefficient of friction (referred to as CCF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, the SiHy contact lens of the present invention preferably has a surface smoothness better than ACUVUE OASYS or ACUVUE TruEye when blinded using the surface smoothness techniques described in Example 1.

In another preferred embodiment, the hydrated SiHy contact lens is preferably highly resistant to finger rubbing, as evidenced by the absence of surface cracking lines visible in the dark field after rubbing the SiHy contact lens with the fingers. It is believed that surface cracking caused by rubbing with fingers may reduce the smoothness of the surface and / or may not be able to prevent the migration of silicon to the surface (impact).

In another preferred embodiment, a hydrated SiHy contact lens of the present invention comprises an inner layer of silicone hydrogel material, an anterior outer hydrogel layer, and a posterior outer hydrogel layer, wherein the anterior and posterior hydrogel layers are of substantially constant thickness and are combined at the outer edge of the contact lens. completely covering the inner layer of the silicone hydrogel material. It should be understood that the first and second outer zones in the cross-sectional modulus profile correspond to the two outer hydrogel layers, and the inner zone corresponds to the inner layer of the silicone hydrogel material. All of the various embodiments of the outer hydrogel layers (crosslinked coating) described above for another aspect of the present invention can be used individually or in any combination in this aspect of the present invention as the outer hydrogel layers. All of the various embodiments of the inner layer of the silicone hydrogel material described above for another aspect of the present invention can be used individually or in any combination in this aspect of the present invention as the inner layer of the silicone hydrogel material.

In accordance with this aspect of the present invention, the outer hydrogel layers have a substantially constant thickness and have a thickness of at least about 0.1 microns, preferably from about 0.1 microns to about 20 microns, more preferably from about 0.25 microns to about 15 microns, even more preferably from about 0.5 microns to about 12.5 microns, most preferably from about 1 microns to about 10 microns. The thickness of each outer hydrogel layer of a SiHy contact lens of the present invention is determined by AFM analysis of the fully hydrated SiHy contact lens section as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is no more than about 30% (i.e., 30% or less), preferably no more than about 20% (20% or less), more preferably no more than about 10% (10% or less) the thickness at the center of the SiHy contact lens in a fully hydrated state. In addition, each of the two outer hydrogel layers is substantially free of silicon (as expressed in atomic percent silicon content of about 5% or less, preferably about 4% or less, even more preferably about 3% or less, based on the content of of all elements, determined by analysis by means of RES contact lens in the dried state), preferably does not contain any silicon. It should be understood that a small amount of silicon may optionally be included (but preferably if not included) in the polymer network of the outer hydrogel layer so that it does not significantly degrade the surface characteristics (hydrophilicity, wettability, and / or surface smoothness) of the SiHy contact lens ...

предпочтительно примерно

, более предпочтительно примерно

еще более предпочтительно примерно

. В альтернативных предпочтительных вариантах осуществления, если WC_Линза составляет примерно 55% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 150%; если WC_Линза составляет примерно 60% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 200%; если WC_Линза составляет примерно 65% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 250%; если WC_Линза составляет примерно 70% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 300%.In another preferred embodiment, the two outer hydrogel layers of the hydrated SiHy contact lens of the present invention have a water content greater than the water content (designated as WC _Lens ) in the hydrated silicone hydrogel contact lens, and more preferably should be no less than about 1 , 2 times (i.e. 120%) exceed WC _Lens . It is contemplated that the water swell ratio for each outer hydrogel layer may roughly correspond to the water content of the outer hydrogel layer, as noted above. If the WC _Lens is about 45% or less, then the water swell ratio for each outer hydrogel layer is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250%, even more preferably at least about 300%. If the WC _Lens exceeds 45%, then the swelling ratio in water for each outer hydrogel layer is at least about

preferably about

, more preferably about

even more preferably about

... In alternative preferred embodiments, if the WC _Lens is about 55% or less, then the water swell ratio for each outer hydrogel layer is at least about 150%; if the WC _Lens is about 60% or less, then the water swelling ratio for each outer hydrogel layer is at least about 200%; if the WC _Lens is about 65% or less, then the water swelling ratio for each outer hydrogel layer is at least about 250%; if the WC _Lens is about 70% or less, then the water swelling ratio for each outer hydrogel layer is at least about 300%.

Preferably, the SiHy contact lens also contains a transition layer located between the silicone hydrogel material and the outer hydrogel layer. All of the various transition layer embodiments described for the previous aspect of the present invention may be used individually or in any combination in this aspect of the present invention.

The hydrated SiHy contact lens of the present invention can be made by the methods described above. All of the various embodiments of the inner layer (i.e., the silicone hydrogel material) described above can be used individually or in any combination in this aspect of the present invention as the silicone hydrogel core. All of the various embodiments described above for the previous aspect of the present invention may be used individually or in any combination in this aspect of the present invention.

It should be understood that while in this aspect of the present invention, various embodiments, including preferred embodiments of the present invention, may be described above separately, they can be combined and / or used together in any desired manner in the method of the present invention to form other embodiments of silicone hydrogel contact lenses of the present invention. All of the various embodiments described above for the previous aspect of the present invention may be used singly or in combination in any desired manner in this aspect of the present invention.

Another aspect of the present invention is a hydrated silicone hydrogel contact lens. The hydrated silicone hydrogel contact lens of the present invention includes: a silicone hydrogel material as a bulk material, an anterior surface and an opposing posterior surface; wherein the contact lens has (1) an oxygen permeability of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 bbl / mm, and (2) a surface smoothness of a critical coefficient of friction (designated as FCC) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, where the front and rear surfaces have a low surface concentration of negatively charged groups, including carboxy groups, characterized by adhesion of no more than about 200 preferably no more than about 160, more preferably no more than about 120, even more preferably no more than about 90, most preferably no more than about 60 positively charged particles in a positively charged particle adhesion study.

In a preferred embodiment, the hydrated silicone hydrogel contact lens has a modulus of elasticity (or Young's modulus) of from about 0.3 MPa to about 1.8 MPa, preferably from about 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa; a water content of about 10% to about 75%, preferably about 10% to about 70%, more preferably about 15% to about 65%; even more preferably from about 20% to about 60%, most preferably from about 25% to about 55 wt. %; surface wettability having an average water contact angle of about 90 ° or less, preferably about 80 ° or less, more preferably about 70 ° or less, even more preferably about 60 ° or less, most preferably about 50 ° or less; hydrophilicity of the surface, characterized by the value of the VVP equal to not less than about 10 s; or combinations thereof.

In another preferred embodiment, the hydrated SiHy contact lens is preferably highly resistant to finger rubbing, as evidenced by the absence of surface cracking lines visible in the dark field after rubbing the SiHy contact lens with the fingers. It is believed that surface cracking caused by rubbing with fingers may reduce the smoothness of the surface and / or may not be able to prevent the migration of silicon to the surface (impact).

In another preferred embodiment, the hydrated SiHy contact lens of the present invention comprises an inner layer of silicone hydrogel material, an anterior outer hydrogel layer, and a posterior outer hydrogel layer, wherein the anterior and posterior hydrogel layers have a substantially constant thickness and are combined at the outer edge of the contact. lenses, completely covering the inner layer of the silicone hydrogel material. It should be understood that the first and second outer zones in the cross-sectional modulus profile correspond to the two outer hydrogel layers, and the inner zone corresponds to the inner layer of the silicone hydrogel material. All of the various embodiments of the outer hydrogel layers (crosslinked coating) described above for another aspect of the present invention can be used individually or in any combination in this aspect of the present invention as the outer hydrogel layers. All of the various embodiments of the inner layer of the silicone hydrogel material described above for another aspect of the present invention can be used individually or in any combination in this aspect of the present invention as the inner layer of the silicone hydrogel material.

In accordance with this aspect of the present invention, the outer hydrogel layers have a substantially constant thickness and have a thickness of at least about 0.1 microns, preferably from about 0.1 microns to about 20 microns, more preferably from about 0.25 microns to about 15 microns, even more preferably from about 0.5 microns to about 12.5 microns, most preferably from about 1 microns to about 10 microns. The thickness of each outer hydrogel layer of a SiHy contact lens of the present invention is determined by AFM analysis of the fully hydrated SiHy section of the contact lens as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably no more than about 30% (i.e., 30% or less), preferably no more than about 20% (20% or less), more preferably no more than about 10% (10 % or less) of the thickness at the center of the SiHy contact lens in a fully hydrated state. In addition, each of the two outer hydrogel layers is substantially free of silicon (as expressed in atomic percent silicon content of about 5% or less, preferably about 4% or less, even more preferably about 3% or less, based on the content of of all elements, determined by analysis by means of RES contact lens in the dried state), preferably does not contain any silicon. It should be understood that a small amount of silicon may optionally be included (but preferably if not included) in the polymer network of the outer hydrogel layer so that it does not significantly degrade the surface characteristics (hydrophilicity, wettability, and / or surface smoothness) of the SiHy contact lens ... To provide a low surface concentration of negatively charged groups (eg, carboxy groups), the front and back hydrogel layers must have a relatively low carboxylic acid content. Preferably, if the front and back hydrogel layers have a carboxylic acid content of about 20 wt. % or less, preferably about 15 wt. % or less, even more preferably about 10 wt. % or less, most preferably about 5 wt. % or less.

предпочтительно примерно

более предпочтительно примерно

еще более предпочтительно примерно

В альтернативных предпочтительных вариантах осуществления, если WC_Линза составляет примерно 55% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 150%; если WC_Линза составляет примерно 60% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 200%; если WC_Линза составляет примерно 65% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 250%; если WC_Линза составляет примерно 70% или менее, то отношение набухания в воде для каждого наружного гидрогелевого слоя составляет не менее примерно 300%.In another preferred embodiment, the two outer hydrogel layers of the hydrated SiHy contact lens of the present invention have a water content greater than the water content (designated as WC _Lens ) in the hydrated silicone hydrogel contact lens, and more preferably should be at least about 1. 2 times (i.e. 120%) the water content (WC _Lens ) in a hydrated silicone hydrogel contact lens. It is contemplated that the water swell ratio for each outer hydrogel layer may roughly correspond to the water content of the outer hydrogel layer, as noted above. If the WC _Lens is about 45% or less, then the water swell ratio for each outer hydrogel layer is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250%, even more preferably at least about 300%. If the WC _Lens exceeds 45%, then the swelling ratio in water for each outer hydrogel layer is at least about

preferably about

more preferably about

even more preferably about

In alternative preferred embodiments, if the WC _Lens is about 55% or less, then the water swell ratio for each outer hydrogel layer is at least about 150%; if the WC _Lens is about 60% or less, then the water swelling ratio for each outer hydrogel layer is at least about 200%; if the WC _Lens is about 65% or less, then the water swelling ratio for each outer hydrogel layer is at least about 250%; if the WC _Lens is about 70% or less, then the water swelling ratio for each outer hydrogel layer is at least about 300%.

In another preferred embodiment, the front and back hydrogel layers independently have a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%. most preferably at least about 40%, relative to the inner layer.

Preferably, the SiHy contact lens also contains a transition layer located between the silicone hydrogel material and the outer hydrogel layer. All of the various transition layer embodiments described for the previous aspect of the present invention may be used individually or in any combination in this aspect of the present invention.

The hydrated SiHy contact lens of the present invention can be made by the methods described above. All of the various embodiments of the inner layer (i.e., the silicone hydrogel material) described above can be used individually or in any combination in this aspect of the present invention as the silicone hydrogel core. All of the various embodiments described above for the previous aspect of the present invention may be used individually or in any combination in this aspect of the present invention.

It should be understood that while in this aspect of the present invention, various embodiments, including preferred embodiments of the present invention, may be described above separately, they can be combined and / or used together in any desired manner in the method of the present invention to form other embodiments of silicone hydrogel contact lenses of the present invention. All of the various embodiments described above for the previous aspect of the present invention may be used singly or in combination in any desired manner in this aspect of the present invention.

The above disclosure enables one of ordinary skill in the art to carry out the present invention. Various modifications, changes, and combinations thereof can be made to the various embodiments described in the present invention. In order for the reader to better understand the preferred embodiments and their advantages, the following examples are presented. It should be understood that the description and examples are typical.

While various embodiments of the present invention have been described using specific terms, devices, and techniques, such descriptions are for illustrative purposes only. The terms used are descriptive and not restrictive. It should be understood that changes and modifications may be made to the present invention by those skilled in the art without departing from its spirit or scope, which is defined by the following claims. In addition, it should be understood that the features of the various embodiments may be transferred in whole or in part from one to another. Therefore, the essence and scope of the appended claims are not limited to the description of the disclosed preferred embodiments.

Example 1

Oxygen permeability measurements

The apparent oxygen permeability of the lens and the oxygen permeability of the lens material are determined in a manner similar to that described in US Pat. No. 5,760,100 and Winterton et al. (The Cornea: Transactions of the World Congress on the Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pp 273-280), which are incorporated herein by reference in their entirety. Oxygen streams (J) are measured at 34 ° C in a wet cell (i.e., the relative humidity of the gas streams is maintained at about 100%) using a Dk ₁₀₀₀ instrument (available from Applied Design and Development Co., Norcross, GA) or similar analytical device. A stream of air having a known oxygen content (for example, 21%) is passed from one side of the lens at a rate of about 10 to 20 cm ³ / min, and a stream of nitrogen is passed from the opposite side of the lens at a rate of about 10 to 20 cm ³ / min. Before the measurement, the sample is brought into equilibrium with the media used in the study (i.e., saline or distilled water) at the temperature set for the study for at least 30 minutes, but not more than 45 minutes. Prior to measurement, any test media used as the top layer shall be equilibrated at the temperature set for the test for at least 30 minutes, but not more than 45 minutes. The speed of the stirring motor is set equal to 1200 ± 50 rpm, which corresponds to the setting of 400 ± 15 of the stepper motor speed controller. Measure the barometric pressure around the system, P _measured . The thickness (t) of the lens in the study area is determined by measuring at about 10 positions with a Mitotoya VL-50 micrometer or similar instrument and averaging the measurements. The oxygen concentration in the nitrogen stream (i.e. oxygen that diffuses through the lens) is measured with a DK1000 instrument. The apparent oxygen permeability of the lens material, Dk _app (in barrels), is determined using the following formula:

in which J = oxygen flow [μl O ₂ / cm ² - min]

P _oxygen = (P _measured - P _{water vapor} ) = (% O ₂ in the air stream) [mm Hg. st.] = partial pressure of oxygen in the air stream

P _measured = barometric pressure (mmHg)

P _{water vapor} = 0 mm Hg. Art. at 34 ° C (dry cell) (mmHg)

P _{water vapor} = 40 mm Hg. Art. at 34 ° C (wet cell) (mmHg)

t = average lens thickness in the study area (mm) Dk _app is expressed in barrels.

The apparent oxygen permeability of a material (Dk / t) can be calculated by dividing the oxygen permeability (Dk _app ) by the average lens thickness (t).

The results of the measurements described above are not corrected for the so-called boundary layer effect, which is attributed to the use of a water or salt bath on the top of the contact lens during oxygen flow measurement. The effect of the boundary layer leads to the fact that the reduced value of the apparent Dk of the silicone hydrogel material is less than the real value of its own Dk. In addition, the relative influence of the boundary layer effect in the case of thinner lenses is greater than in the case of thicker lenses. As a result, the reduced Dk value varies with lens thickness when it should be constant.

The lens's intrinsic Dk value can be determined based on the Dk value corrected for the surface resistance to oxygen flow due to the influence of the boundary layer as follows.

Apparent oxygen permeability values (one value) were measured using the same equipment for reference lenses lotrafilcon A (Focus® N & D® from VISION CORPORATION USA) or lotrafilcon B (AirOptix ™ from VISION CORPORATION USA). Reference lenses have the same optical power as the lenses under test and measurements are taken at the same time as the test lenses.

Using the same equipment, oxygen flow through a set of lotrafilcon A or lotrafilcon B (reference) lenses of different thickness is measured using the apparent Dk method described above and the intrinsic Dk (Dk _i ) of the reference lens is obtained. The set of thicknesses should cover a range of about 100 microns or more. Preferably, the range of reference lens thicknesses includes the thicknesses of the lenses under study. The Dk _app value for these reference lenses should be measured with the same equipment as for the test lenses, and ideally the measurements are taken simultaneously with the test lenses. During the experiment, the equipment settings and measurement parameters must be constant. If desired, measurements can be made several times for each sample.

Determine the oxygen residual resistance, R _r , from the reference lens using Equation 1 for the calculations.

where t denotes the thickness of the lens under study (i.e., the reference lens) and n denotes the number of reference lenses under study. The dependence of the value of the residual resistance for oxygen, R _r on the values of t is plotted and approximated by the dependence of the form Y = a + bX, where for the lens j, Y _j = (ΔP / J) _j and X = t _j . Residual resistance for oxygen, R _r is equal to a.

The residual oxygen resistance determined above is used to calculate the corrected oxygen permeability Dk _c (estimated intrinsic Dk) for the lenses under study using Equation 2.

The estimated intrinsic Dk of the lens under study can be used to calculate what the apparent Dk (Dk _{a_std} ) will be at a standard lens thickness in the same test medium using Equation 3. The standard thickness (t _std ) of lotrafilcon A = 85 μm. The standard thickness of lotrafilcon is B = 60 microns.

Ion Permeability Measurements

The ion permeability of a lens is determined by the procedures described in US Pat. No. 5,760,100 (which is incorporated herein by reference in its entirety. The ion permeability values given in the following examples are relative diffusion coefficients of Ionoflux (D / D _ref ) compared to the reference lens material, which is Alsacon, Alsacon has an Ionoflux diffusion coefficient of 0.314 × 10 ^-3 mm ² / min.

Determination of surface smoothness

Surface smoothness is determined by a quantitative ranking scheme in which 0 is assigned to the polyacrylic acid coated control lens and 4 is assigned to commercially available Air Optix ™ lenses. The samples are washed with an excess of distilled at least 3 times and then transferred to the PFP before testing. Before examination, hands are washed with a soap solution, rinsed thoroughly with distilled water, and then dried with KimWipe® wipes. The samples are held between the fingers and the numerical value is determined for each sample by comparison with the above standard lenses described above. For example, if lenses are found to be only slightly better than Air Optix ™ lenses, they are assigned the number 3. To ensure consistency, all definitions are independently the same two operators to eliminate bias and to ensure that previous data show very good qualitative agreement. and consistency in estimates.

Studies of the hydrophilicity / wettability of the surface. The water contact angle on a contact lens is a general measure of the surface hydrophilicity (or wettability) of a contact lens. In particular, a smaller water contact angle corresponds to a more hydrophilic surface. Fixed-drop average contact angles of contact lenses using a VCA 2500 XE contact angle device available from AST, Inc., Boston, Massachusetts. With the help of this equipment it is possible to measure the advancing or receding contact angles or non-changing (static) contact angles. Measurements for fully hydrated contact lenses and immediately after drying the drops are carried out as follows. The contact lens is removed from the vessel and washed 3 times with ~ 200 ml of fresh distilled water to remove loosely bound packaging additives from the lens surface. Then the lenses are placed on top of a clean, lint-free cloth (Alpha Wipe TX1009), thoroughly blotted to remove the water on the surface, fixed on a device for measuring the contact angle of wetting, blown with a stream of dry air until dry, and finally, using the method of a stationary drop, automatically determine the contact angle wetting using the software provided by the manufacturer. The distilled water used to measure the contact angle has an electrical resistivity of> 18 MΩ.cm and the volume of the used drop is 2 μL. Typically, uncoated silicone hydrogel lenses (after autoclaving) have a fixed drop measurement of about 120 °. Before contact with contact lenses, the tweezers and the stand are thoroughly rinsed with isopropanol and rinsed with distilled water.

Investigations of the time of destruction of the water film (WFD). The hydrophilicity of the lens surface (after autoclaving) is assessed by determining the time required before the water film on the lens surface begins to break. Briefly, the technique is as follows: remove the lenses from the vessel and rinse 3 times with ~ 200 ml of fresh distilled water to remove loosely bound packaging additives from the lens surface. The lens is removed from the solution and held in front of a bright light source. Visually assess the time it takes to break the water film (breakdown in wetting) when the underlying lens material is exposed. On uncoated lenses, the film usually disintegrates immediately after being removed from distilled water and is set to have an ERVP of 0 s. Lenses with an EVVP ≥5 s are considered to have good hydrophilicity and are also expected to have sufficient tear film retention in the eye.

Coating integrity studies. The integrity of the coating on the surface of a contact lens can be examined using the Sudan Black Staining Procedure described below. Coated contact lenses (PSL coating, plasma coating or any other coating) are immersed in a solution of Sudan Black (Sudan Black in oil with Vitamin E) dye. Sudan black dye is hydrophobic and has a strong tendency to adsorb to a hydrophobic material either on the hydrophobic lens surface or hydrophobic areas of a hydrophobic lens that has been partially coated (eg, a silicone hydrogel contact lens). If the coating on the hydrophobic lens is intact, no colored areas are observed on or inside the lens. All test lenses are fully hydrated.

Coating durability studies. The lenses are finger-rubbed 30 times using Solo-care® Universal Lens Care Solution and then rinsed with saline. This procedure is repeated a predetermined number of times, for example, from 1 to 30 times (i.e., a number of finger rubbing tests are repeated sequentially, which simulates the cycles of cleaning and soaking with a liquid). The lenses are then tested with Sudan Black (ie, the coating integrity test described above) to determine if the coating is still intact. Finger rubbing should not significantly increase the amount of stained areas to be successful (for example, stained areas should not cover more than about 5% of the entire lens surface). To determine the durability of the coating, the contact angles of water wetting are measured.

Determination of the content of azetidinium groups. The content of azetidinium groups in PAE can be determined using one of the methods described below.

Research with the help of VNSC. The charge density for PAE (i.e., the content of azetidinium groups) can be determined by investigation using VNSC, a colorimetric titration in which the titrating reagent is potassium vinyl sulfate (VNSC) and the indicator is toluidine blue. See publication, S-K Kam and J. Gregory, "Charge determination of synthetic cationic polyelectrolytes by colloid titration," in Colloid & Surface A: PhysiCOChem. Eng. Aspect 159: 165-179 (1999). VNSC binds positively charged particles, for example, toluidine blue and azetidinium groups of PAE. The decrease in the intensity of absorption of toluidine blue is proportional to the charge density of the PAE (the content of azetidinium groups).

Research using PES-Na. The PES-Na study is another colorimetric titration technique for determining the charge density of PAE (the content of azetidinium groups). In this study, the titrating reagent is sodium polyethylene sulfonate (PES-Na) instead of BNSC. The study is similar to the VNSC study described above.

PCD-04, выпускающегося фирмой BTG. Принципы определения с помощью этого детектора приведены на сайте в интернете фирмы BTG http://www.btg.com/products.asp?langage=1&appli=5&numProd=357&cat=prod).Research using PCD. The PCD study is a potentiometric titration to determine the charge density of the PAE (the content of azetidinium groups). The titrating reagent is sodium polyethylene sulfonate (PES-Na), VNSC or another titrating reagent. AET is determined using an electrode, for example, using a particle charge detector

PCD-04 manufactured by BTG. The principles of determination using this detector are given on the BTG website http://www.btg.com/products.asp?langage=1&appli=5&numProd=357&cat=prod).

NMR technique. Active positively charged fragments in PAE are azetidinium groups (AGG). In the method for determining the ratio using NMR, the ratio of the number of protons of the RAG to the number of protons not related to the RG is determined. This ratio is an indicator of the charge density or ADH in the AET.

Investigation of dirt adhesion. Contact lenses with a highly charged surface can be heavily adhered to by the patient when they are used. A paper towel is rubbed between gloved hands and then both sides of the lens are rubbed with fingers to transfer dirt to the lens surface. The lens is then rinsed briefly and then viewed through a microscope. Each lens is rated on a quality scale from 0 (dirt does not adhere) to 4 (dirt adhesion is equivalent to adhesion to a PAA coated control lens). Lenses rated "0" or "1" are considered acceptable.

Example 2

Obtaining the CE-PDMS macromer

At the first stage, α, ω-bis (2-hydroxyethoxypropyl) -polydimethylsiloxane (Mn = 2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate (IPDI) according to the reaction 49.85 g of α, ω-bis (2-hydroxyethoxypropyl) - polydimethylsiloxane with 11.1 g of IPDI in 150 g of dry methyl ethyl ketone (MEK) in the presence of 0.063 g of dibutyltin dilaurate (DBODL). The reaction mixture was incubated for 4.5 h at 40 ° C to obtain IFDI-PDMS-IFDI. At the second stage, 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 a solution of IPDI-PDMS-IPDI, in to which another 0.063 g of DBODL was added. The reactor is incubated for 4.5 hours at about 40 ° C. and HO-PDMS-IFDI-PDMS-IFDI-PDMS-OH is obtained. Then the MEK is removed under reduced pressure. In the third step, the terminal hydroxy groups are capped with methacryloyloxyethyl groups by the addition of 7.77 g of isocyanatoethyl methacrylate (IEM) and another 0.063 g of DBODL to obtain IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (i.e. CE-PDMS with terminal methacrylate groups ).

Alternative preparation of CE-PDMS macromer with methacrylate end groups

240.43 g of KF-6001 are added to a 1 L reactor equipped with stirrer, thermometer, cryostat, dropping funnel and nitrogen / vacuum line adapter, and then dried under high vacuum (2 x 10 ^-2 mbar). Then, in an atmosphere of dry nitrogen, 320 g of distilled MEK are added to the reactor and the mixture is thoroughly mixed. 0.235 g of DBTDL is added to the reactor. Then the reactor is heated to 45 ° C, with moderate stirring through an addition funnel for 10 minutes, 45.86 g of IFDI are added to the reactor. The reaction mixture is kept for 2 h at 60 ° C. Then add 630 g of KF-6002, dissolved in 452 g of distilled MEK, and mix until a homogeneous solution is formed. 0.235 g DBODL was added and the reactor was kept at about 55 ° C overnight under dry nitrogen. The next day the MEK is removed by rapid distillation. The reactor is cooled and 22.7 g of IEM are added 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 next day, the reaction mixture is cooled to about 18 ° C to obtain a CE-PDMS macromer containing terminal methacrylate groups.

Example 3

Obtaining compositions for lenses

The composition for the lens is prepared by dissolving a composition of the following composition in 1-propanol: 33 wt. % of the CE-PDMS macromer obtained in example 2, 17 wt. % N- [tris (trimethylsiloxy) -silylpropyl] acrylamide (TRTS-Am), 24 wt. % N, N-dimethylacrylamide (DMA), 0.5 wt. % sodium salt of N- (carbonylmethoxypolyethylene glycol-2000) -1,2-distearoyl-sn-glycero-3-phosphoethanolamine) (L-PEG), 1.0 wt. % Darocur 1173 (DC1173), 0.1 wt. % dye for visible tinting, (5% dispersion of blue pigment, copper phthalocyanine in tris (trimethylsiloxy) silylpropyl methacrylate, TRIS) and 24.5 wt. % 1-propanol.

Lenses making

Lenses are made by injection molding from the lens composition obtained above in a reusable mold similar to that shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The mold includes a concave mold half made from CaF ₂ and a convex mold half made from PMMA. The source of UV radiation is a Hamamatsu lamp with a WG335 + TM297 bandpass filter with an intensity of about 4 mW / cm ² . The formulated lens composition is irradiated with UV light for about 25 seconds. Injection molded lenses are extracted with isopropanol (or methyl ethyl ketone, MEK), washed in water, and coated with polyacrylic acid by dipping the lenses into a PAA solution in propanol (0.1 wt%, acidified with formic acid to about pH 2.5) and hydrated in water. It has been found that lenses made containing a reactive PAA-PSL base coat have the following characteristics: ion permeability of about 8.0 to about 9.0 relative to Alsacon lens material; the apparent Dk (one value) is approximately 90 to 100; the water content is from about 30 to about 33%; and the bulk modulus is from about 0.60 MPa to about 0.65 MPa.

Example 4

A saline solution for packaging coating (IPC) is prepared by adding 0.2% polyamidoamine-epichlorohydrin (PAE) (Kymene, available from Ashland as an aqueous solution, and it is used as obtained, according to NMR, the content of azetidinium groups is 0, 46) in phosphate buffered saline (abbreviation PFF is used below) (about 0.044 w / w% NaH ₂ PO ₄ ⋅H ₂ O, about 0.388 w / w /% Na ₂ HPO ₄ ⋅ 2H ₂ O, about 0.79 w / w% NaCl) and then the pH is adjusted to 7.2-7.4.

The lenses made in Example 3 were placed in polypropylene lens packs containing 0.6 ml of IPC saline (half of the IPC saline was added before placing the lens). The blister was then sealed with foil and autoclaved for about 30 minutes at 121 ° C to form crosslinked coatings (PAA-x-PAE coating) on the lenses.

Dirt adhesion, surface cracking, surface smoothness, contact angle and water film destruction time (WFD) are then determined for the lenses. Test lenses (packed / autoclaved in NPU saline, i.e. lenses containing PAK-PSL coating) are free of dirt, while control lenses (packed / autoclaved in PFP, i.e. lenses containing reactive PAK-PSL base coat) contain a lot of adhering dirt. The contact angle of water wetting (SWR) of the lenses under study is small (~ 20 °), but the WVTR is less than 2 s. When examined with a dark-field microscope, after use of the lenses, lines of severe cracking (inversion of the lenses and rubbing with fingers) are visible. The test lenses are much less smooth than the control lenses, as evidenced by the qualitative finger rubbing test.

Example 5

Partial sodium salt of acrylamide-acrylic acid copolymer (PAAm-PAA or AAM copolymer with AA, solids content ~ 80%,) (80/20), Mw. 520,000, Mn 150,000) were purchased from Aldrich and used as received.

NPU saline is prepared by dissolving 0.02% copolymer of AAM with AA (80/20) and 0.2% PAE (Kymene, manufactured by Ashland as an aqueous solution and used as received, according to NMR the content of azetidinium groups is 0, 46) in the ZFF. The pH is adjusted to 7.2 ~ 7.4. PFP is obtained by dissolving 0.76% NaCl, 0.044% NaH ₂ PO ₄ ⋅H ₂ O and 0.388% Na ₂ HPO ₄ ⋅ 2H ₂ O in water.

Lenses containing the reactive PAK-PSL basecoat prepared in Example 3 were placed in polypropylene lens packs containing 0.6 ml of NPU saline (half of the saline was added prior to lens placement). The blister is then sealed with foil and autoclaved for about 30 minutes at about 121 ° C. It is believed that a crosslinked coating consisting of three layers of PAA-x-PAE-x-copolymer AAM with AA is formed on the lenses during autoclaving.

The test lenses (packed / autoclaved in NPU saline, i.e. lenses containing PAA-x-PAE-x-copolymer AAM with AA) do not contain adhering dirt after wiping with a paper towel. The lenses under study have an ERVP exceeding 10 s. When examining with a dark-field microscope, cracking lines are visible after wiping the studied lenses. The test lenses are much smoother than the test lenses made in Example 4, but still not as smooth as the control lenses packed in the PFF.

Example 6

NPU saline is prepared by dissolving 0.02% copolymer of AAM with AA (80/20) and 0.2% PAE (Kymene, manufactured by Ashland as an aqueous solution and used as received, according to NMR the content of azetidinium groups is 0, 46) in the PFF and setting the pH value equal to 7.2 ~ 7.4. The brine is then treated by heating it at about 70 ° C. for 4 hours (heat pretreatment). During this heat pretreatment, the copolymer of AAM with AA and PAE partially crosslinks with each other (i.e., all azetidinium groups contained in the PAE are not consumed) to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups in the branched polymer mesh in NPU saline solution. After thermal pretreatment, the finished IPC saline is filtered using a 0.22 µm polyethersulfone (PES) membrane filter and cooled to room temperature.

Lenses containing the reactive PAK-PSL basecoat prepared in Example 3 were placed in polypropylene lens packs containing 0.6 ml of NPU saline (half of the saline was added prior to lens placement). The blister is then sealed with foil and autoclaved for about 30 minutes at about 121 ° C. to form a crosslinked coating (PAA-x-hydrophilic polymer material) on the lenses.

The lenses under study (packaged in pre-heat-treated NPU saline, i.e. lenses coated with PAA-x-hydrophilic polymer material), after wiping with a paper towel, do not contain adhered dirt, while the control lenses (packaged in PFF, t i.e. lenses containing a non-covalently bonded PAA layer) contain a lot of adhered dirt. The lenses under study have an ERVP exceeding 10 s. When examined with a dark-field microscope, no cracking lines are detected after wiping the lenses. The test lenses are very smooth and are equivalent to the control lenses according to the finger rubbing test.

A series of experiments was carried out to study the effect of the conditions (duration and / or temperature) of the pre-heat treatment of the NPU saline solution on the surface characteristics of the lenses made containing the NPU saline solution coating. Heat treatment for about 6 hours or more at about 70 ° C produces lenses that are susceptible to dirt adhesion to a degree similar to that of control lenses. It is assumed that a longer pre-heat treatment can lead to the consumption of most of the azetidinium groups, and the amount of azetidinium groups remaining in the network of the branched polymer obtained from the obtained water-soluble polymer material is insufficient for attaching the polymer material to the PAA coating. Heat treatment for only 4 hours at 50 ° C gives lenses, on the surface of which, using a dark field microscope, after rubbing with fingers, cracking lines are found, similar to those observed for the studied lenses in example 5, when the IPC saline solution was not subjected to preliminary heat treatment. It is assumed that a shorter pre-heat treatment can lead to the consumption of a small amount of azetidinium groups, and the amount of azetidinium groups remaining in the network of the branched polymer obtained from the water-soluble polymer material is large enough that the resulting crosslinked coating (PAA-x-hydrophilic polymer material) on the lenses could have too high crosslinking density.

Example 7

Partial sodium salt of acrylamide-acrylic acid copolymer (solids content ~ 90%, AAM copolymer with AA 90/10, Mw 200,000) was purchased from Polysciences, Inc. and used as received.

NPU saline is prepared by dissolving 0.07% PAAm-PAA (90/10) and 0.2% PAE (Kymene, available from Ashland as an aqueous solution and used as received, NMR azetidinium content of 0.46 ) in the PFF and the establishment of the pH value equal to 7.2-7.4. The brine is then heat pretreated for about 4 hours at about 70 ° C. (heat pretreatment). During this heat pretreatment, the copolymer of AAM with AA and PAE partially crosslinks with each other (i.e., all azetidinium groups contained in the PAE are not consumed) to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups in the branched polymer mesh in NPU saline solution. After thermal pretreatment, the NPU saline is filtered using a 0.22 µm polyethersulfone [PES] membrane filter and cooled to room temperature.

Lenses containing the reactive PAA-PSL basecoat prepared in Example 3 and uncoated Lotrafilcon B lenses (manufactured by VISION CORPORATION, USA) immersed in an acidic propanol solution of PAA (about 0.1%, pH ~ 2.5) placed in polypropylene lens packs containing 0.6 ml of heat-pretreated NPU saline (half of the NPU saline is added before placing the lens). The blister is then sealed with foil and autoclaved for about 30 minutes at 121 ° C. to form a crosslinked coating (PAA-x-hydrophilic polymer material) on the lenses.

The test lenses (Lotrafilcon B and the lenses made in Example 3 containing PAA-x-hydrophilic polymer) did not contain any adhering dirt after wiping with a paper towel. The lenses under study have an ERVP exceeding 10 s. When examined with a dark-field microscope, no cracking lines are detected after rubbing the lenses with fingers. Qualitative finger rubbing has shown that the lenses are very smooth.

Example 8

For experiments, NPU saline solutions are prepared containing from about 0.05% to about 0.09% PAAm-PAA and from about 0.075% to about 0.19% PAE (Kymene, available from Ashland as an aqueous solution and used in the resulting form, according to NMR, the content of azetidinium groups is equal to 0.46) in the PFP. The NPU saline solutions are heat-treated for 8 hours at 60 ° C and the lenses made in Example 3 are packed in heat-pretreated NPU saline solutions. There is no difference in surface characteristics of finished lenses and all lenses have excellent surface smoothness, dirt adhesion resistance, excellent wettability and no signs of surface cracking.

Example 9

For the experiments, NPU saline solutions are prepared containing about 0.07% PAAm-PAA and a sufficient amount of PAE, with an initial content of azetidinium groups equal to about 8.8 mmoleq / L (~ 0.15% PAE). The pre-heat treatment conditions in the main experimental scheme are such that the temperature varies in the range from 50 ° C to 70 ° C and the duration of the pre-reaction varies in the range from about 4 to about 12 hours. The pre-treatment for 24 hours at 60 ° C was also investigated. WITH. Then 10 ppm is added to the brine. hydrogen peroxide to prevent microflora growth and NPU saline solutions are filtered using a 0.22 µm polyethersulfone [PES] membrane filter with openings.

The lenses made in Example 3 were packaged in pre-heat treated IPC saline solutions and then the blisters were autoclaved for 45 minutes at 121 ° C. All lenses have excellent surface smoothness, wettability and surface cracking resistance. Some lenses show dirt from paper towels adhering, as shown in Table 1.

Example 10

Copolymers of methacryloyloxyethylphosphorylcholine (MPC) with one vinyl monomer containing carboxy groups (CH ₂ = CH (CH ₃ ) C (O) OC ₂ H ₄ OC (O) C ₂ H ₄ COOH (MS), methacrylic acid (MC)) in the absence or in the presence of butyl methacrylate (BMA) is tested in packaging coating systems in combination with PAE.

Prepare a PFF containing NaCl (0.75 wt%), NaH ₂ PO ₄ ⋅H2O (0.0536 wt%), Na ₂ HPO ₄ ⋅2H ₂ O (0.3576 wt%) and distilled water (97 , 59 wt%) and 0.2% PAE (polycup 3160) was added. The pH is adjusted to about 7.3.

Then, to obtain an IPC saline solution, 0.25% of one of several copolymers of IPC is added and the IPC saline solution is subjected to preliminary heat treatment at 70 ° C for 4 hours to form a water-soluble thermally crosslinkable hydrophilic polymer material containing azetidinium groups. After 4 hours, the heat-pretreated NPU saline is filtered through 0.22 μm polyethersulfone (PES) membrane filters (Fisher Scientific catalog # 09-741-04, Thermo Scientific nalgene # 568-0020 (250 ml) ...

Lenses containing the reactive PAA-PSL basecoat prepared in Example 3 were packaged in a pre-heat treated IPC saline solution and autoclaved for about 30 minutes at 121 ° C. Table 2 shows that all lenses have excellent surface characteristics.

Example 11

PAA coated lenses. Lenses, made by injection molding from the lens composition obtained in example 3, according to the injection molding procedure described in example 3, were extracted and coated by immersion in the following series of baths: 3 MEK baths (22, 78 and 224 sec); distilled water bath (56 s); 2 baths of PAA coating solution (prepared by dissolving 3.6 g of PAA (molecular weight: 450 kDa, manufactured by Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds separately; and 3 baths with distilled water, each for 56 seconds.

PAE / PAK coated lenses. The lenses made above, containing the base coat of PAA, are sequentially immersed in the following baths: 2 baths with a solution for coating PAA, which is obtained by dissolving 0.25 wt. % PAE (Polycup 172, manufactured by Hercules) in distilled water and adjusting the pH to about 5.0 with sodium hydroxide and finally filtering the resulting solution using a 5 µm filter for 44 and 56 seconds, respectively; and 3 baths with distilled water, each for 56 seconds. After this treatment, the lenses contain one PAA layer and one PAE layer.

Lenses coated with PAK-x-PAE-x-SMS. One batch of lenses, which contain one PAA layer and one PAE layer, are packed in 0.2% sodium carboxymethylcellulose (CMC, Product # 7H 3SF PH, Ashland Aqualon) in phosphate buffered saline (PBS) and then the pH is adjusted to 7.2-7.4. The blisters are then sealed and autoclaved for about 30 minutes at 121 ° C. to form crosslinked coatings (PAK-x-PAE-x-CMC) on the lenses.

Lenses coated with PAK-x-PAE-x-GK. Another batch of lenses, which contain one PAA layer and one PAE layer, are packaged in a 0.2% solution of hyaluronic acid (HA, Product # 6915004, Novozymes) in phosphate buffered saline (PBS) and then the pH is adjusted to 7.2- 7.4. The blisters are then sealed and autoclaved for about 30 minutes at 121 ° C. to form crosslinked coatings (PAA-x-PAE-x-HK) on the lenses.

Lenses made with a coating of PAK-x-PAE-x-CMC or coated with PAK-x-PAE-x-GK are not stained with Sudan Black, do not contain adhering dirt and, according to microscopic examination, do not contain cracks. Lenses coated with PAK-x-PAE-x-SMS have an average contact angle of 30 ± 3 °, while lenses coated with PAK-x-PAE-x-GK have an average contact angle of 20 ± 3 ° ...

Example 12

Obtaining an NPU solution. The reaction mixture is obtained by dissolving 2.86 wt. % mPEG-SH 2000 (methoxy-poly (ethylene glycol) thiol, average MW 2000, Product # MPEG-SH-2000, Laysan Bio Inc.), together with 2 wt. % PAE (Kymene, manufactured by Ashland as an aqueous solution and used as received, the NMR content of azetidinium groups is 0.46) in PBS and the final pH is adjusted to 7.5. The solution is heat treated for about 4 hours at 45 ° C. (heat pretreatment). During this heat pretreatment, mPEG-SH 2000 and PAE interact with each other to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups and chemically grafted polyethylene glycol polymer chains. After heat treatment, the solution is diluted 10-fold with a PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2-7.4, and then filtered using a 0.22 μm polyether sulfone (PES ) membrane filter. The prepared NPU saline solution contains 0.286 wt. % hydrophilic polymeric material (containing about 59 wt.% MPEG-SH-2000 chains and about 41 wt.% PAE chains) and 0.25% sodium citrate dihydrate. PFP is obtained by dissolving 0.74% NaCl, 0.053% NaH ₂ PO ₄ ⋅H ₂ O and 0.353% Na ₂ HPO ₄ , 2H ₂ O in water.

Lenses with stitched coatings. The PAA coated lenses made in Example 11 were packaged in the above IPC saline solution in polypropylene lens packs and then autoclaved for about 30 minutes at about 121 ° C. to form a crosslinked coating on the lenses.

Finished lenses do not contain any adhering dirt or cracks after wiping the lenses. The lenses were found to be very smooth in the finger rubbing test, in contrast to the PAA coated control lenses.

A series of experiments was carried out to study the effect of conditions (reaction duration and concentration of the mPEG-SH2000 solution (at a constant concentration of PAE equal to 2%) on the surface characteristics of the obtained lenses containing a coating of NPU saline solution. The results are shown in Table 3.

Increasing the concentration of the mPEG-SH 2000 solution improves the smoothness of the lens surface. It is assumed that an increase in the contact angle of the surface wetting may be due to an increase in the density of terminal metal groups on the surface due to an increase in the density of crosslinks. At a high crosslink density, corresponding to a solution concentration of 0.6%, the contact angle approaches the value obtained on flat substrates to which a polyethylene glycol (PEG) monolayer is grafted (Literature: Langmuir 2008, 24, 10646-10653).

Example 13

A series of experiments were conducted to study the effect of the molecular weight of mPEG-SH. NPU saline was prepared according to the procedure described in Example 12. However, the following mPEG-SH were used to prepare the saline: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000 and mPEG-SH 20000. All saline solutions were heat treated at 45 ° C for 4 hours and diluted 10 times. The results and reaction conditions are shown below:

Example 14

The reaction mixture is prepared by dissolving 2.5% methoxy-poly (ethylene glycol) thiol, average MW 2000 (Product # MPEG-SH-2000, Laysan Bio Inc.), 10% PAE (Kymene) in PBS and 0.25% dihydrate sodium citrate. This final solution is then adjusted to pH 7.5 and also degassed to minimize thiol oxidation by passing nitrogen for 2 hours. This solution is then heat treated for about 6 hours at 45 ° C. to form a thermally crosslinkable hydrophilic polymer material containing MPEG-SH-2000 groups chemically grafted to the polymer by reaction with azetidinium groups contained in the PAE. After heat treatment, the solution was diluted 50-fold with PBS containing 0.25% sodium citrate, adjusted to pH 7.2 ~ 7.4, and then filtered using 0.22 μm polyether sulfone (PES ) membrane filter. The finished NPU saline solution contains about 0.30 wt. % polymeric material (containing about 17 wt.% MPEG-SH-2000 and about 83 wt.% PAE) and 0.25% sodium citrate dihydrate.

The PAA coated lenses made in Example 11 were packaged in the above IPC saline solution in polypropylene lens packs and then autoclaved for about 30 minutes at about 121 ° C. to form a crosslinked coating on the lenses.

Finished lenses do not contain any adhering dirt or cracks after wiping the lenses. The test lenses were found to be very smooth in the finger rubbing test, in contrast to the PAA coated control lenses.

Example 15

The reaction mixture is prepared by dissolving 3.62% mPEG-NH ₂ 550 (methoxy-poly (ethylene glycol) -amine, molecular weight ~ 550 (Product # MPEG-NH ₂ -550, Laysan Bio Inc.) together with 2% PAE (Kymene manufactured by Ashland in the form of an aqueous solution and used as received, the NMR content of azetidinium groups is 0.46) in the PBS and the final pH is adjusted to 10. The solution is heat treated for about 4 hours at 45 ° C to form thermally crosslinkable hydrophilic polymer material containing MPEG-NH2-550 groups chemically grafted to the polymer by reaction with azetidinium groups contained in the PAE.After thermal treatment, the solution is diluted 10 times with PBS containing 0.25% sodium citrate, pH value set to 7.2-7.4 and then filtered using a 0.22 μm polyethersulfone (PES) membrane filter. 0.562 wt. % polymeric material (containing 64 wt.% MPEG-SH-2000 and about 36 wt.% PAE) and 0.25% sodium citrate dihydrate. PFP is obtained by dissolving 0.74% NaCl, 0.053% NaH ₂ PO ₄ ⋅H ₂ O and 0.353% Na ₂ HPO ₄ , 2H ₂ O in water.

The PAA coated lenses made in Example 11 were packaged in the above IPC saline solution in polypropylene lens packs and then autoclaved for about 30 minutes at about 121 ° C. to form a crosslinked coating on the lenses.

Finished lenses are free of adhering dirt and cracks after wiping the lenses (with your fingers).

Example 16

et al., CHIMIA, 53 (1999), 269-274, во всей своей полноте включена в настоящее изобретение в качестве ссылки). Примерно 2,5% звеньев винилового спирта в nelfilcon А модифицированы N-(2,2-диметоксиэтил)акриламидом.Poloxamer 108 (sample) and nelfilcon A (USA VISION) were used as received. Nelfilcon A is a polymerizable polyvinyl alcohol prepared by modifying polyvinyl alcohol (e.g. Gohsenol KL-03, manufactured by Nippon Gohsei, etc.) with N- (2,2-dimethoxyethyl) acrylamide under cyclic acetal formation conditions (

et al., CHIMIA, 53 (1999), 269-274, in its entirety incorporated into the present invention by reference). Approximately 2.5% of the vinyl alcohol units in nelfilcon A are modified with N- (2,2-dimethoxyethyl) acrylamide.

NPU saline is prepared by dissolving 0.004% poloxamer 108, 0.8% nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1% disodium hydrogen phosphate (dihydrate) in distilled water. The brine is subjected to a preliminary heat treatment by stirring for 2 hours at about 65-70 ° C. After thermal pretreatment, the saline solution is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

The lenses made in Example 3 were placed in polypropylene lens packs containing 0.6 ml of NPU saline (half of the saline was added prior to placing the lens). The blister is then sealed with foil and autoclaved for about 30 minutes at 121 ° C.

The lenses under study, after wiping with a paper towel, do not contain any adhering dirt. The lenses have an ERVP of more than 10 s. When examined with a dark-field microscope, no cracking lines are detected after rubbing the lenses with fingers. The lenses are much smoother than the lenses made in Example 4, but still not as smooth as the PAA coated control lenses packed in the PFF.

Example 17

A. Synthesis of 80% Ethylene Functionalized Chain Extended Polysiloxane

KF-6001A (α, ω-bis (2-hydroxyethoxypropyl) -polydimethylsiloxane, Mn = 2000, manufactured by Shin-Etsu) and KF-6002A (α, ω-bis (2-hydroxyethoxypropyl) -polydimethylsiloxane, Mn = 3400, manufactured Shin-Etsu) are individually dried at about 60 ° C. for 12 hours (or overnight) under high vacuum in a one-necked flask. The molar equivalent mass of OH for KF-6001A and KF-6002A is determined by titration of hydroxy groups and used to calculate the millimolar equivalent for use in the synthesis.

The 1 L reaction vessel is evacuated overnight to remove moisture and filled with dry nitrogen. 75.00 g (75 meq.) Of Dried KF6001A is placed in a reactor and then 16.68 g (150 meq.) Of freshly distilled IPDI are added to the reactor. The reactor was purged with nitrogen and heated to 45 ° C. with stirring, and then 0.30 g of DBTDL was added. The reactor is sealed and the hydrogen flow is maintained at a positive pressure. Heat evolution occurs, after which the reaction mixture is allowed to cool and stirred at 55 ° C for 2 hours. Then 248.00 g (150 meq) of dried KF6002A is added to the reactor at 55 ° C and then 100 μl of DBTDL is added. The contents of the reactor were stirred for 4 hours. The heating was stopped and the reactor was allowed to cool overnight. The nitrogen purge is stopped and the reactor is vented with moderate stirring for 30 minutes. A hydroxy-terminated, chain-extended polysiloxane containing 3 polysiloxane segments, HO-PDMS-IFDI-PDMS-IFDI-PDMS-OH (or HO-CE-PDMS-OH) is formed.

To obtain 80% ethylene functionalized polysiloxane, 18.64 g (120 meq.) IEM are added to the reactor along with 100 μl DBODL. The contents of the reactor were stirred for 24 hours and then the product (80% IEM-capped CE-PDMS) was decanted and stored in a refrigerator.

B: Synthesis of a non-UV absorbing amphiphilic branched polysiloxane prepolymer

A 1 L reactor is equipped with a 500 ml dropping funnel, overhead stirrer, reflux condenser with nitrogen / vacuum line adapter, thermometer and sampling adapter. The reactor was charged with 45.6 g of 80% IEM-capped CE-PDMS obtained above and sealed. A solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, 27.80 g of (tris (trimethylsilyl)) -siloxypropyl) methacrylate (TRIS) in 279 g of ethyl acetate is placed in an addition funnel. The reactor is degassed at <1 mbar for 30 min at RT using a high vacuum pump. The monomer solution is degassed at 100 mbar and RT for 10 min using 3 cycles, filling the reactor with nitrogen between degassing cycles. Then the monomer solution is placed in the reactor and then the reaction mixture is stirred and heated to 67 ° C. Upon heating, a solution of 1.50 g of mercaptoethanol (chain transfer reagent, RPC) and 0.26 g of azoisobutyronitrile in 39 g of ethyl acetate are placed in an addition funnel and deoxygenated three times at 100 mbar, RT for 10 min. When the reactor temperature becomes 67 ° C., the initiator / PCR solution is added to the PDMS / monomer solution in the reactor. The reaction was allowed to proceed for 8 hours and then the heating was stopped and the temperature of the reactor was brought to room temperature within 15 minutes.

Then the resulting reaction mixture is siphoned into a dry single-necked flask with a sealed lid and 4.452 g of IEM with 0.21 g of DBTDL is added. The mixture was stirred for 24 hours at room temperature to obtain a non-UV absorbing amphiphilic branched polysiloxane prepolymer. To a solution of this mixture was added 100 μl of a solution of piperonyloxyhydroxytetramethylene in ethyl acetate (2 g / 20 ml). The solution is then concentrated to 200 g (~ 50%) using a rotary evaporator at 30 ° C and filtered through filter paper with a pore size of 1 μm. After replacing the solvent with 1-propanol, the solution is further concentrated to the required concentration.

C. Synthesis of UV absorbing amphiphilic branched polysiloxane prepolymer

A 1 L reactor is equipped with a 500 ml dropping funnel, overhead stirrer, reflux condenser with nitrogen / vacuum line adapter, thermometer and sampling adapter. Then, 45.98 g of 80% IEM-capped CE-PDMS obtained above are placed in the reactor and the reactor is sealed. A solution of 0.512 g HEMA, 25.354 g DMA, 1.38 g Norbloc methacrylate, 26.034 g TRIS in 263 g ethyl acetate is placed in an addition funnel. The reactor is degassed at <1 mbar for 30 min at RT using a high vacuum pump. The monomer solution is degassed at 100 mbar and RT for 10 min using 3 cycles, filling the reactor with nitrogen between degassing cycles. Then the monomer solution is placed in the reactor and then the reaction mixture is stirred and heated to 67 ° C. When heated, a solution of 1.480 g of mercaptoethanol (chain transfer agent, RPC) and 0.260 g of azoisobutyronitrile are dissolved in 38 g of ethyl acetate, placed in an addition funnel and deoxygenated three times at 100 mbar and room temperature for 10 minutes. When the reactor temperature becomes 67 ° C., the initiator / PCR solution is added to the PDMS / monomer solution in the reactor. The reaction was allowed to proceed for 8 hours and then the heating was stopped and the temperature of the reactor was brought to room temperature within 15 minutes.

Then the resulting reaction mixture is siphoned into a dry single-necked flask with a sealed lid and 3.841 g of isocyanatoethyl acrylate with 0.15 g of DBTDL are added. The mixture was stirred for 24 hours at room temperature to obtain a UV absorbing amphiphilic branched polysiloxane prepolymer. To a solution of this mixture was added 100 μl of a solution of piperonyloxyhydroxytetramethylene in ethyl acetate (2 g / 20 ml). The solution is then concentrated to 200 g (-50%) using a rotary evaporator at 30 ° C. and filtered through filter paper with a pore size of 1 μm.

D-1: Lens Composition Containing Non-UV Absorbing Polysiloxane Prepolymer

In a flask of yellow glass with a volume of 100 ml add 4.31 g of the synthesized solution of macromer obtained in example C-2 (82.39% in 1-propanol). In a flask with a volume of 20 ml, 0.081 g of TPO and 0.045 g of DMPC are dissolved in 10 g of 1-propanol and then transferred to the macromer solution. The mixture is then concentrated to 5.64 g using a rotary evaporator at 30 ° C., 0.36 g of DMA is added and the composition is homogenized at room temperature. 6 g of clear lens composition D-1 are obtained.

D-2: Lens composition containing UV absorbing polysiloxane prepolymer (4% DMA)

In a 100 ml yellow glass flask, 24.250 g of the macromer solution obtained in Example D-2 (43.92% in ethyl acetate) was added. In a flask with a volume of 50 ml, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of Solvent is removed using a rotary evaporator at 30 ° C., then 20 g of 1-propanol is added. After two cycles, the mixture is concentrated to 14.40 g. To this mixture, 0.6 g of DMA is added and the composition is homogenized at room temperature. 15 g of clear lens composition D-2 is obtained.

D-3: Lens composition containing UV absorbing polysiloxane prepolymer (2% DMA / 2% HEA)

To a 100 ml yellow glass flask, add 24.250 g of the macromer solution obtained in Example D-2 (43.92% in ethyl acetate). In a flask with a volume of 50 ml, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of Solvent is removed using a rotary evaporator at 30 ° C., then 20 g of 1-propanol is added. After two cycles, the mixture is concentrated to 14.40 g. To this mixture, 0.3 g of DMA and 0.3 g of HEA are added and the composition is homogenized at room temperature. 15 g of clear lens composition D-3 is obtained.

Example 18

Example E: Covalent Bonding of Coated Modified PAE Polymers

Monomers containing amino groups, N- (3-aminopropyl) methacrylamide hydrochloride (APMAA-HCl) or N- (2-aminoethyl) methacrylamide hydrochloride (AEMAA-HCl) are purchased from Polysciences and used as received. Poly (amidoamine epichlorohydrin) (PAE) is obtained from Ashland as an aqueous solution and used as received. Copolymer of acrylamide and acrylic acid (90/10) from Polysciences, mPEG-SH from Laysan Bio and copolymer of MPC and AEMA (i.e. copolymer of methacryloyloxyethylphosphorylcholine (MPC) with aminoethyl methacrylate (AEMA), available from as received.

APMAA-HCl monomer was dissolved in methanol and added to lens compositions D-1, D-2 and D-3 (prepared in Example 17) to a concentration of 1 wt. %.

Reactive packaging brine is prepared by dissolving the components listed in Table 4, along with suitable buffering salts, in distilled water. The brine is pre-heat treated by stirring for 8 hours at about 60 ° C. After thermal pretreatment, the saline solution is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

Lens composition D-1 prepared in Example 17 was modified by adding APMAA-HCl monomer (stock solution of APMMA-HCL in a 1: 1 mixture of methanol: propanol) and cured at 16 mW / cm ² using a 330 nm filter. Lens compositions D-2 and D-3 prepared in Example 17 were modified by addition of APMAA-HCl monomer and cured at 4.6 mW / cm ² using a 380 nm filter.

DSM lenses. The concave portions of the polypropylene lens molds are filled with about 75 μl of the lens composition prepared above and the molds are closed with the convex portions of the polypropylene lens molds (base curvature mold). Contact lenses are prepared by curing in closed molds for about 5 minutes with a UV source (Hamamatsu lamp with a filter with a bandwidth limited to 330 nm with an intensity of about 16 mW / cm ² .

LS lenses. LS lenses are made by injection molding from the lens composition obtained above in a reusable form similar to that shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The mold includes a concave mold half made from CaF ₂ and a convex mold half made from PMMA. The source of UV radiation is a Hamamatsu lamp with a limited passband up to 380 nm and an intensity of approximately 4.6 mW / cm ² . The formulated lens composition is irradiated with UV light for about 30 seconds.

Lens composition D-1, modified with APMAA-HCl, is cured according to the procedures described above for DSM and LS, and lens composition D-2 or D-3 is cured according to the procedures described above for LS.

The molded lenses are extracted with methyl ethyl ketone, hydrated and packaged in one of the saline solutions described in Table 5. The lenses are placed in polypropylene lens packs containing 0.6 ml of IPC saline (half of the saline is added prior to placing the lens). The blister is then sealed with foil and autoclaved for 30 minutes at 121 ° C.

Examination of the lens surfaces shows that all lenses tested are free of adhering dirt after wiping with a paper towel. When examined with a dark-field microscope, no cracking lines are detected after rubbing the lenses with fingers.

Lens surface wettability (LSS), surface smoothness and contact angle were determined and the results are shown in Table 5. Lenses were made according to the DSM method, unless otherwise indicated. Surface smoothness is rated on a quality scale of 0 to 5, with lower values indicating greater surface smoothness. Typically, after being coated in a package, the surface characteristics of the lens are improved.

The number refers to the packing brine number shown in Table 4.

LS lenses

Example 19

Obtaining compositions for lenses. A lens composition is prepared by dissolving a composition of the following composition in 1-propanol: about 32 wt. % of the CE-PDMS macromer obtained in example 2, about 21 wt. % TRIS-Am, about 23 wt. % DMA, about 0.6 wt. % L-PEG, about 1 wt. % DC1173, about 0.1 wt. % dye for visible tinting (5% blue pigment dispersion, copper phthalocyanine in TRIS), about 0.8 wt. % DMPC, about 200 ppm H-tempo and about 22 wt. % 1-propanol.

Lens manufacturing. Lenses are made by injection molding from the lens composition obtained above into a reusable mold (quartz concave mold half and glass convex mold half) similar to the mold shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The lens composition in the molds is irradiated with UV light (13.0 mW / cm ² ) for about 24 seconds.

PAA solution for coating. A PAA coating solution is prepared by dissolving an amount of PAA (molecular weight: 450 kDa, available from Lubrizol) in a given volume of 1-propanol sufficient to obtain a concentration of about 0.36 wt. %, and the pH value with formic acid is adjusted to about 2.0.

PAA coated lenses. Injection molded contact lenses such as above are extracted and coated by immersion in the following series of baths: distilled water bath (approximately 56 seconds); 6 IEC baths (approximately 44, 56, 56, 56, 56 and 56 s, respectively); a bath with distilled water (about 56 s); one bath with PAA solution to form a coating (about 0.36-0.44 wt.%, acidified with formic acid to about pH 1.7-2.3) in 100% 1-propanol (about 44 seconds); one bath with a mixture of water / 1-propanol 50% / 50% (about 56 s); 4 baths of distilled water, each for about 56 seconds; one bath with PFF for about 56 s; and one bath of distilled water for about 56 seconds.

NPU saline solution. Partial sodium salt of AAM-AA copolymer (~ 90% solids, AAM-AA copolymer 90/10, Mw 200,000) was purchased from Polysciences, Inc. and used as received. PAE (Kymene, according to NMR the content of azetidinium groups is 0.46) is purchased from Ashland in the form of an aqueous solution and used as received. NPU saline is prepared by dissolving about 0.07% w / w. copolymer AAM with AA (90/10) and about 0.15% PAE (the initial content of azetidinium groups is about 8.8 mmol) in PBS (about 0.044 w / w% NaH ₂ PO ₄ ⋅H ₂ O, about 0.388 w / w /% NaHPO _{4 ⋅2H 2} O, about 0.79 w / w% NaCl) and adjusting the pH to 7.2 ~ 7.4. The IPC saline is then heat pretreated for about 4 hours at about 70 ° C (heat pretreatment) During this heat pretreatment, the AAM-AA copolymer and PAE are partially crosslinked to each other (i.e., all azetidinium groups are not consumed contained in PAE) to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups in a branched polymer network in an NPU saline solution. After thermal pretreatment, the NPU saline is filtered using a 0.22 µm PES membrane filter and cooled to room temperature. Then 10 ppm is added to the finished IPC saline solution. hydrogen peroxide to prevent microflora growth and NPU saline are filtered using a 0.22 µm PES membrane filter.

Crosslinked coating application. The lenses containing the reactive PAK-PSL basecoat obtained above are placed in polypropylene lens packs (one lens per section) containing 0.6 ml of IPC saline (half of the saline is added before the lens is placed). The blisters are then sealed with foil and autoclaved for about 30 minutes at about 121 ° C. to provide SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymer material).

Investigation of the characteristics of SiHy lenses. Contact lenses made by SiHy, on which there are crosslinked coatings (PAA-x-hydrophilic polymer material), after wiping with a paper towel, do not contain any adhering dirt, while control lenses (packed in PFF, i.e. lenses containing a non-covalently bound PAA layer) contain a lot of adhering dirt. The lenses have an oxygen permeability (Dk _c or estimated intrinsic Dk) of 146 barrels, a bulk modulus of about 0.76 MPa, and a water content of about 32 wt. %, relative ion permeability of about 6 (compared to the Alsacon lens), contact angle of about 34 to 47 °, and WEP longer than 10 s. When examined with a dark-field microscope, no cracking lines are detected after wiping the lenses. The lenses are very smooth and are equivalent to the control lenses according to the finger rubbing test.

Example 20

The autoclavable SiHy lenses and IPC salines in lens packs obtained in Examples 6, 14 and 20 were studied using the biocompatibility described below.

In vitro cytotoxicity study. SiHy lenses were tested using the USP Direct Contact Material Assay (USP - United States Pharmacopoeia). Lens extracts were tested by USP MEM Elution and ISOCEN Cell Growth Inhibition Assay, and NPU saline in packs after autoclaving was tested by modified elution technique. All lenses and lens extracts tested met the acceptance criteria for each study and no unacceptable cytotoxicity was observed.

In vivo study. The ISO mouse systemic toxicity study shows that mice do not exhibit systemic toxicity with the lens extracts. ISO eye irritation studies in rabbits indicate that lens extracts are not considered irritating to rabbit eye tissue. An ISO eye irritation study in rabbits indicates that the NPU saline in autoclavable packs is not considered irritating to rabbit eye tissue. Lenses that are worn and removed daily for 22 consecutive days are non-irritating in the rabbit model and the eyes exposed to the test lenses are similar to the eyes exposed to the control lenses. An ISO sensitization study (Guinea Pig Maximization Testing of Packaging Solutions) shows that NPU saline after autoclaving does not cause any delayed skin sensitization in guinea pigs. The Guinea Pig Maximization Testing of Lens Extracts (ISO) shows that sodium chloride and sesame oil lens extracts do not cause delayed skin sensitization in guinea pigs.

Genotoxicity study. IPN saline solutions from lens packaging and SiHy lens extracts were studied using reverse mutation studies in bacteria (Ames test) and it was found that lens extracts and IPN saline solutions were considered non-mutagenic in relation to the investigated Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WPuvrA. Extracts of SiHy lenses were studied using the study of micronuclei of erythrocytes of mammals and it was found that they do not have clastogenic activity and give a negative result in the study of micronuclei in the bone marrow of mice. IPH saline solutions from lens packaging have been studied using a Chinese hamster ovary chromosome aberration study and found not to induce structural and numerical aberration of Chinese hamster ovary cell chromosomes in non-activated and S9-activated research systems. Extracts of SiHy lenses were studied using a gene mutation study (murine lymphoma mutagenesis study) and it was found that lens extracts were negative in a murine lymphoma mutagenesis study.

Example 21

Surface composition of preformed SiHy contact lenses (i.e., SiHy contact lens without any coating and before application of PAA base coat), SiHy contact lenses with PAA coating (i.e. lenses before sealing and autoclaving in lens packaging saline NPU) and SiHy contact lenses on which there is a crosslinked coating, which are all made according to the methods described in example 20, determined by examining vacuum-dried contact lenses using X-ray electron spectroscopy (RES). RES is a technique for studying the composition of the surface of lenses with a depth of investigation equal to about 10 nm. The surface compositions of the three types of lenses are shown in Table 6.

Table 6 shows that when a PAA coating is applied to a SiHy lens (preformed, uncoated), the carbon and oxygen content is close to that of PAA (60% C and 40% O) and the silicon content is significantly reduced (from 12, 1% to 4.5%). If a crosslinked coating is additionally applied to the PAA coating, then carbon, nitrogen and oxygen are predominantly present on the surface (excluding hydrogen, since the RES does not register hydrogen on the surface). These results indicate that the topmost layer of the SiHy contact lens, on which the crosslinked coating is located, is likely mainly composed of a hydrophilic polymer material that is the reaction product of the AAM copolymer with AA (90/10) (60% C, 22% O and 18 % N) and PAE.

A RES study was also carried out on the following commercially available SiHy lenses that were vacuum dried. The surface compositions of these commercially available SiHy contact lenses are shown in Table 7.

The SiHy contact lens of the present invention has been found to have a nominal surface silicon content of about 1.4%, much less than commercially available SiHy lenses without plasma coatings (Acuvue® Advance®, Acuvue® Oasys ®, TruEye ™, Biofinity®, Avaira ™) and PureVision® (plasma oxidized) and Premio ™ (unknown plasma treated), and even smaller than SiHy lenses with a plasma deposited coating thickness of approximately 25 nm (N & D® Aqua and Air Optix® Aqua ™). This very low Si content is comparable to the control, polyethylene from Goodfellow (LDPE (low density polyethylene), d = 0.015 mm; LS356526 SDS; ET31111512; 3004622910). These results indicate that the very low ESD value obtained for the vacuum dried SiHy contact lens of the present invention may be due to contamination introduced during manufacture, including vacuum drying and ESD examination, as well as the content fluoride in lenses that do not contain fluoride. Silicon is effectively shielded from interaction when examined with RES in SiHy contact lenses of the present invention.

A study was also carried out using RES SiHy contact lenses proposed in the present invention (made according to the methods described in example 20), commercially available SiHy contact lenses (CLARITI ™ 1 Day, ACUVUE® TruEye (narafilc on A and narafilcon B)), polyethylene sheet manufactured by Goodfellow (LDPE, d = 0.015 mm; LS356526 SDS; ET31111512; 3004622910), DAILIES® (polyvinyl alcohol hydrogel lenses, i.e. non-silicone hydrogel lenses), ACUVUE® Moist (hydrogel lenses, methacrylate i.e. non-silicone hydrogel lenses). All lenses are vacuum dried. Polyethylene sheets, DAILIES® and ACUVUE® Moist were used as controls as they do not contain silicon. The contents of silicon atoms in the surface layers of the test samples are as follows: 1.3 ± 0.2 (polyethylene sheet); 1.7 ± 0.9 (DAILIES®); 2.8 ± 0.9 (ACUVUE® Moist); 3.7 ± 1.2 (three SiHy lenses were made according to the methods described in example 20); 5.8 ± 1.5 (CLARITI ™ 1 Day); 7.8 ± 0.1 (ACUVUE® TruEye ™ (narafilcon A)); and 6.5 ± 0.1 (ACUVUE® TruEye ™ (narafilcon B)). The results for the SiHy contact lens of the present invention are closer to those for conventional hydrogels than for silicone hydrogels.

Example 22

PAK with fluorescent label (PAK-F).

PAA-F is synthesized in the laboratory by covalently linking 5-aminofluorescein with PAA (Mw 450k). The content of the fluorescein label is a few percent, for example, about 2 mol. % (or n / (m + n) = 2% in the formula below)

Fluorescently labeled PAA (PAA-F) X: fluorescein moiety

Lenses making

Lenses were made by injection molding from the lens composition obtained above in Example 19 in a reusable mold (quartz concave mold half and glass convex mold half) similar to the mold shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The lens composition in the molds is irradiated with UV light (13.0 mW / cm ² ) for about 24 seconds.

PAK-F coating solution

A PAK-F coating solution is obtained by dissolving the amount of PAA-F obtained above in a given volume of a 1-PrOH / water (95/5) solvent mixture to form a concentration of about 0.36 wt. %, and the pH value with formic acid is adjusted to about 2.0. To dissolve PAK-F, approximately 5% water is used.

PAK coated lenses

The injection molded contact lenses are extracted and coated by immersion in the following series of baths: distilled water bath (approximately 56 seconds); 6 baths with IEC (approximately 44, 56, 56, 56, 56 and 56 s, respectively); a bath with distilled water (about 56 s); one bath with a PAK-F coating solution (about 0.36 wt.%, acidified with formic acid to about pH 2.0) in 1-PrOH / water (95/5) solvent mixture (about 44 s); one bath with a mixture of water / 1-propanol 50% / 50% (about 56 s); 4 baths of distilled water, each for about 56 seconds; one bath with PFF for about 56 s; and one bath of distilled water for about 56 seconds.

Crosslinked coating

Lenses containing the reactive PAK-PSL basecoat obtained above are placed in polypropylene lens packs (one lens in one section) containing 0.6 ml of NPU saline prepared according to the procedures described in Example 19 (half of the saline is added to lens placement). The blisters are then sealed with foil and autoclaved for about 30 minutes at about 121 ° C. to provide SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymer material).

Confocal laser fluorescence microscopy

A cross-section of a hydrated SiHy lens containing a crosslinked coating (obtained above) is cut and placed between two glass slides and images are collected using a confocal laser fluorescence microscope (model # Zeiss LSM 510 Vis). Scan from the front curved side of the lens to the back curved side of the lens or in the opposite direction. The presence of PAK-F is detectable by green fluorescence and confocal laser fluorescence microscopic images can be obtained. Examination of confocal laser fluorescence microscopic images shows that the PAK-F-enriched layer is located on both lens surfaces (front and back surfaces) and on the outer edge, while no PAK-F is found in the bulk material of the hydrated lens.

The fluorescence intensity profiles are examined along the cross-section of the lens along a line passing through the back and front surfaces and perpendicular to the back surface. FIG. 3 shows two typical profiles of fluorescence intensity along two lines over the lens section, one at the point at which the lens thickness is approximately 100 μm (Fig.3A), and the second at the point at which the lens thickness is approximately 200 μm (Fig.3B) ... The starting points in FIG. 3 are the center points between the front and back surfaces along these lines. It may be noted that in FIG. 3, there is a layer enriched with PAK-F near the boundary surfaces of the SiHy lens, on which the cross-linked coating is located, PAK-F is not contained in the volume of the lens and the coating thickness is almost the same on these two sections, regardless of the section thickness.

The thickness of the PAA-F-enriched layer (i.e. the sum of the diffusion depth into the outer hydrogel layer and the depth of penetration of PAA-F into the bulk material (i.e. the inner layer)), or the transition layer (in the schematic illustration in Fig. 2 , transition layer 115) can be determined from the fluorescence intensity profile shown in FIG. 3. The possible thickness of the transition layer (enriched with PAK-F layer) is determined by the distance from zero intensity after crossing the peak intensity and back to zero intensity. Given that unknown factors (such as scattering) can contribute to the fluorescence intensity, the minimum layer thickness is the thickness for which the fluorescence intensity remains at least 10% of the maximum peak intensity. Based on this assessment, the minimum thickness of the PAA-F enriched layer may be at least about 5 microns. Note that the thickness of the PAA coated SiHy lenses made in the previous examples can be greater, since the PAA concentration used is 10 times greater than the PAA-F concentration used in the described experiments. A thicker coated lens can also be obtained by using an immersion duration greater than 44 s, in this experiment the PAK-F immersion time used is 44 s. Thicker coated lenses can also be obtained by using PAA having different molecular weights.

Example 23

This example illustrates the determination of the water content of a crosslinked coating (two outer hydrogel layers) on SiHy according to the present invention). To evaluate the possible water content in the crosslinked SiHy coating of the lenses made in Example 19, samples of the polymer containing the coating components were prepared for testing. The resulting gels are then hydrated and the water content is determined.

The solutions are prepared using two polymer components of the crosslinked coating obtained in example 19: copolymer of AAM with AA (90/10) and PAE to obtain the following composition: 12.55% w / w. PAE, 6.45% w / w copolymer AAM with AA (90/10) and 81% w / w. water. The PAE / AAM / AA copolymer ratio is the same as the NPU saline ratio in Example 19, but the concentration of the individual components is higher to ensure gel formation during autoclaving.

The solution is then autoclaved for about 45 minutes at 121 ° C, after which a sample gel is formed. Then gel samples are prepared for determination of water content by examining the samples after hydration (n = 3). Hydrated samples are prepared by immersing the gel sample in SoftWear saline for at least about 6 hours (i.e., hydrate overnight).

The hydrated samples are blotted dry and the hydrated weight is recorded by weight balance. After registering the hydrated mass, all samples are placed in a vacuum oven at about 50 ° C and dried under <1 inHg vacuum. during the night.

The dried samples are removed from the vacuum oven after overnight drying and the dry weight is then recorded. The water content is calculated as follows:

Water content = (wet weight - dry weight) / wet weight 100%

The water content in the samples was found to be 84.6 ± 0.4 w / w%.

It is believed that this water content in this PAE hydrogel / AAM-AA copolymer characterizes the outer hydrogel layer (crosslinked coating) of the SiHy contact lenses made in Example 19 for the following reasons. First, it is reasonable to assume that the lens's hydrophobic bulk polymers (silicone hydrogel) are not in the outer surface layer. This seems to be a very good assumption based on the RES data. According to the XPS data given in Example 21, the surface of the SiHy lens on which the crosslinked coating is located does not contain silicon or its content is very low, and this shows that the outer surface layer consists almost entirely of coating polymers (PAE and PAAm-PAA). Second, a polyacrylic acid (PAA) basecoat (transition layer) is likely to have a minimal effect on the surface water content. This assumption may be wrong. However, if any charged PAA were contained in the outer surface layer, it would further increase the water content, which would exceed 84.6%. Third, to obtain the PAE / copolymer AAM with AA hydrogel, a much higher concentration of PAE and PAAm-PAA is required than that used in the NPU saline solution in Example 19. This can lead to a higher density of crosslinks in the PAE / AAM copolymer with AA hydrogel, which can lead to artificially low water content. It is assumed that the presence of PAA in the outer hydrogel layer and a lower density of crosslinks due to a lower concentration of polymer materials and crosslinking (in example 19) can lead to a surface layer (outer hydrogel layer) with a water content that is even higher than that established in the studies in this example. It can be assumed that the outer coating layer of the SiHy contact lenses made in Example 19 contains at least 80% water and may contain even more when fully hydrated.

Example 24

An Abbe refractometer is commonly used to measure the refractive index of contact lenses. The difference in refractive indices of the lens under study and the prism of the instrument results in a specific angle of total internal reflection, which results in a dark visible shadow line. The angle at which this shadow line appears is directly related to the refractive index of the lens under study. Most contact lenses (including the uncoated SiHy contact lenses made in Example 19) produce a clear shadow line in the Abbe refractometer, but the SiHy on which the crosslinked coating is located (i.e. the outer hydrogel layers) made in Example 19 does not produce a clear shadow lines. It is believed that this phenomenon is due to a decrease in the refractive index of the lens at the surface relative to the volume and the fact that the transition from volume to surface is not abrupt. It is also assumed that near the surface of the lens, the water content begins to increase, resulting in a local decrease in the refractive index of the lens. This leads to the simultaneous formation of shadow lines at several angles, resulting in a blurred image of the shadow line.

The data obtained with the Abbe refractometer shows that the outer surface layer is characterized by a decrease in water content near the surface of the lens, which is consistent with the results described in example 23.

Example 25

SiHy contact lenses containing the crosslinked coating (i.e. outer hydrogel layers) obtained in Example 19 are desalted in ultrapure water, individually placed in 50 ml disposable beakers containing 50 ml of ultrapure water, and frozen by placing the beaker in a bath with solid carbon dioxide and isopropyl alcohol. The beakers are wrapped with aluminum foil and placed in a VirTis Freezemobile 35EL under vacuum at a pressure of 30 μbar and a refrigerator temperature of -70 ° C. After 24 hours, the aluminum foil is removed to increase heat transfer and the beakers are held for an additional 24-48 hours to remove residual moisture. The beakers are closed to exclude moisture from the air prior to analysis. The lens samples are cut in half and then 2 strips are cut from the middle of each half and fixed at the edges to visualize the sections. The samples were then spray coated with Au / Pd for ~ 1 min and examined by SEM using a Bruker Quantax Microanalysis System (JEOLJSM-800LV SEM). The stand with the sample is tilted ~ 0-60 ° at the discretion of the analyst and the required orientation of the sample is ensured.

It is believed that if SiHy contact lenses are freeze-dried, the hydrated surface structure of the lens may be retained or blocked to a certain extent. FIG. 4A is a top view of an SEM image of the surface of a freeze-dried SiHy contact lens made in Example 19. FIG. 4, it can be seen that the freeze-dried SiHy contact lens has a spongy surface structure as would be expected for a hydrogel with a high water content. This result also confirms that the SiHy contact lens of the present invention contains two outer hydrogel layers with a high water content in the hydrogel. FIG. 4B and 4C are cross-sectional side views of the freeze-dried SiHy contact lens of FIG. 4A. FIG. 4B and 4C show a thick inner layer having a smooth surface, a transition layer (PAA layer) with a bright color above the inner layer, and an outer hydrogel layer with a spongy structure above the transition layer. Based on the data shown in FIG. 4B and 4C, the thickness of the freeze-dried outer hydrogel layer is estimated to be from about 2 microns to about 2.5 microns.

Example 26

Copolymer of AAM with AA (90/10) with a fluorescent label (referred to as PAAm-PAK-F).

PAAm-PAK-F is synthesized in the laboratory by covalently linking 5-aminofluorescein with PAAm-PAA (90/10) in a manner similar to that used to prepare PAA-F. Partial sodium salt of AAM-AA copolymer (~ 90% solids, AAM-AA copolymer 90/10, Mw 200,000) was purchased from Polysciences, Inc. and used as received. The content of the fluorescein label is about 0.04 mol. %.

Modified NPU saline solution using PAAm-PAK-F

This saline was prepared according to the same procedure for the preparation of NPU as described in Example 19, with the difference that PAAm-PAA was replaced by PAAm-PAA-F.

PAK coated lenses

Lenses were made by injection molding from the lens composition obtained in Example 19 above into a reusable mold (quartz concave mold half and glass convex mold half) similar to the mold shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The lens composition in the molds is irradiated with UV light (13.0 mW / cm ² ) for about 24 seconds. The injection molded contact lenses are extracted and coated by immersion in the following series of baths: distilled water bath (approximately 56 seconds); 6 IEC baths (approximately 44, 56, 56, 56, 56 and 56 s, respectively); a bath with distilled water (about 56 s); one bath with PAA solution to form a coating (about 0.36 wt.%, acidified with formic acid to about pH 2.0) in 1-PrOH solvent (about 44 s); one bath with a mixture of water / 1-propanol 50% / 50% (about 56 s); 4 baths of distilled water, each for about 56 seconds; one bath with PFF for about 56 s; and one bath of distilled water for about 56 seconds.

Crosslinked coating

The lenses containing the PAA basecoat obtained above are placed in polypropylene lens packs (one lens per section) containing 0.6 ml of the modified NPU saline solution prepared above using PAAm-PAA-F (half of the saline is added prior to placement lenses). The blisters are then sealed with foil and autoclaved for about 30 minutes at about 121 ° C. to provide SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymer material).

Confocal laser fluorescence microscopy

A piece of a hydrated SiHy lens containing a crosslinked coating (obtained above) is cut and placed between two glass slides and images are collected using a confocal laser fluorescence microscope (model # Zeiss LSM 510 Vis). Scan from the front curved side of the lens to the back curved side of the lens or in the opposite direction. The presence of PAAm-PAK-F is detectable by green fluorescence and confocal laser fluorescence microscopic images can be obtained. Examination of confocal laser fluorescence microscopic images shows that the PAAm-PAA-F-enriched layer (i.e. outer hydrogel layers) is present on both lens surfaces (front and back surfaces) and on the outer edge, whereas in the bulk material of the hydrated lens PAAm-PAK-F is not detected.

The fluorescence intensity profiles are examined along the cross-section of the lens along a line passing through the back and front surfaces and perpendicular to the back surface. The thickness of the PAAm-PAA-F enriched layer can be determined from the fluorescence intensity profile across the lens. The possible thickness of the outer hydrogel layer (enriched with PAAm-PAA-F layer) is determined by the distance from zero intensity after crossing the peak intensity and back to zero intensity. Given that unknown factors (such as scattering) can contribute to the fluorescence intensity, the minimum layer thickness is the thickness for which the fluorescence intensity remains at least 10% of the maximum peak intensity. Based on this assessment, the minimum thickness of the PAAm-PAA-F-enriched layer (hydrated outer hydrogel layer) can be at least about 5 microns.

Example 27

Lenses were made using lens composition D-2 (Example 17) to which APMAA monomer was added at a concentration of 1%. LS lenses are made by injection molding from the lens composition obtained above in a reusable form similar to that shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The mold includes a concave mold half made of glass and a convex mold half made of quartz. The source of UV radiation is a Hamamatsu lamp with a limited passband up to 380 nm and an intensity of approximately 4.6 mW / cm ² . The formulated lens composition is irradiated with UV light for about 30 seconds.

Injection molded lenses are extracted with methyl ethyl ketone (MEK), washed in water, coated with polyacrylic acid by immersing the lenses in a PAA solution in propanol (0.0044 wt%, acidified with formic acid to about pH 2.5) and hydrated in water.

An IPC saline solution of the composition described in Example 9 was prepared by pre-reacting for 8 hours at about 60 ° C. The lenses are placed in polypropylene lens packs containing 0.6 ml of NPU saline (half of the saline is added prior to placing the lens). The blister is then sealed with foil and autoclaved for 30 minutes at 121 ° C.

Examination of the lens surfaces shows that all lenses tested are free of adhering dirt. When examined with a dark-field microscope, no cracking lines are detected after rubbing the lenses with fingers. The lens surface wettability (LWP) is greater than 10 seconds, the surface smoothness is rated "1" and the contact angle is approximately 20 °.

Example 28

The contact lenses made in Example 19 by injection molding SiHy (without any coating) were used. All lenses are extracted with MEK overnight to ensure that any remaining monomer is removed. The first group of lenses (lenses on which a hydrated crosslinked coating is located) is soaked overnight in a PAA solution to obtain a coating (0.36 wt% PAA in 1-propanol, a pH value of 1.7-2.3, established by formic acid), and the second group of lenses (control) is soaked in 1-propanol for the same time. Both sets of lenses were packaged in the IPC saline prepared in Example 19 and autoclaved. Lenses after autoclaving are examined (in groups of 5) using gravimetric analysis to determine the weights of dry and wet contact lenses (N = 14 for the first group of contact lenses; N = 18 for the second group of contact lenses). The results are shown in Table 8.

There is a statistically significant difference (7 mg) in wet weights for the first and second groups of contact lenses, which is due to the presence of a hydrated crosslinked contact lens coating in contrast to the control lenses (uncoated). However, the difference in dry weight for the first and second contact lens groups is about 0.3 mg and is not statistically significant. The water content of the coated lens can be estimated to be ~ 96% using the following calculation

It should be understood that the water content estimated in this case for the crosslinked coating on the contact lens may not be accurate because the difference in dry mass for the first and second groups of contact lenses is too small or even less than the standard deviation.

Example 29

This example shows how to quantify the surface smoothness of SiHy contact lenses using the tilted plate technique (Derby Friction Characterization). The tilted plate technique is a simple technique using the setup shown in FIG. 5. The setup for the tilted plate technique includes a plastic reservoir or tank 501 that is filled with phosphate buffered saline (PBS, pH ~ 7.3) 502, a borosilicate glass plate 503, and a stand 506 whose height is adjustable from 5 mm to 20 mm. mm. Borosilicate glass plate 503 and stand 506 are immersed in phosphate buffered saline 502 in a plastic reservoir or tank 501. During examination, contact lens 504 is placed on a borosilicate glass plate and then a 505 stainless steel cylinder is placed on it (to create physiologically acceptable pressure) ...

где θ обозначает критический угол, F_N обозначает перпендикулярно направленную силу и F_t обозначает касательную силу. Наибольший угол, при котором линза начинает скользить после толчка, но останавливается или скользит до конца в течение более 10 с, определяют, как "критический угол θ". Критический коэффициент трения (ККОТ) является тангенсом критического угла θ. Линза, которая не движется, находится под углом, меньшим критического, а линза, которая не останавливается на этом пути, находится под углом, большим критического. Углы, превышающие критический или меньшие критического, исключают из анализа. Определение характеристик трения по Дерби может являться прямым путем изменения кинематического коэффициента трения.Critical coefficient of friction =

where θ denotes a critical angle, F _N denotes a perpendicular force and F _t denotes a tangential force. The largest angle at which the lens begins to slide after being pushed, but stops or slides all the way for more than 10 seconds, is defined as the "critical angle θ". The critical coefficient of friction (CFC) is the tangent of the critical angle θ. A lens that does not move is at an angle less than the critical one, and a lens that does not stop along the way is at an angle greater than the critical one. Angles greater than critical or less than critical are excluded from the analysis. Derby friction characteristics can be determined directly by changing the kinematic coefficient of friction.

In a tilted plate test, all lenses are stored in the PBS solution for at least overnight (> 6 hours) prior to testing to remove any remaining packing solution. The glass plate (6 "x 4" borosilicate glass) is wiped with a soap solution (1% Micro-90) and wiped off (AlphaWipe TX1009). Each plate is thoroughly rinsed in distilled water for approximately 2 minutes. The friction of the plate is checked by rubbing it with a finger to ensure that all the soap solution has been removed. The water is wiped off with paper towels (KimTech Kimwipe # 34705) and inspected for light to ensure that no debris remains on the glass. The glass plate is placed on racks of different heights in a plastic reservoir or tank and the height of the plate is measured with a micrometer and recorded. The reservoir is filled with phosphate buffered saline (PBS) so that the lens is completely immersed in it (28 mm depth).

Each lens is placed on the "start line" and a 0.79 g cylinder (1/4 inch stainless steel to create a physiologically acceptable pressure) is placed on the surface of the lens. The lens is allowed to slide over the plate and the time it takes for the lens to travel a distance of 96 mm is recorded.

The lens is placed on the "start line" and the weight is removed prior to re-examination. For better repeatability, this preload effect should be minimized. The lens can be examined from many angles and a perfect CCOT can be obtained.

For the 16 commercially available contact lenses and silicone hydrogel contact lenses made in Example 19, the CCT was determined and the results are shown in Table 9. The results show that the SiHy contact lens of the present invention (made in Example 19 and containing a crosslinked coating), has the lowest CCOT of all grades of silicone hydrogel lenses commercially available and researched, and thus has the highest surface smoothness.

KB: Critical height; KU: Critical angle

Example 30

This example shows how to characterize the negatively charged surface of a SiHy contact lens when investigating the adhesion of positively charged particles.

The surface charge of a lens surface can be determined indirectly by its interaction with charged particles or balls. A negatively charged surface attracts positively charged particles. A surface that does not contain a negative charge or does not generally contain a negative charge does not attract positively charged particles or attracts a small amount of positively charged particles.

, где М_СООН обозначает массу карбоксигруппы и M_AA обозначает массу акриловой кислоты). Сшитое покрытие на контактных линзах, изготовленных в примере 14 теоретически не содержит карбоксигрупп, а сшитое покрытие контактных линз, изготовленных в примере 19, может обладать низкой поверхностной концентрацией карбоксигрупп (должно быть меньше, чем

Линзы погружают в дисперсию положительно заряженных частиц, после соответствующей промывки визуализируют частицы, прилипшие к линзе, и оценивают или подсчитывают их количество.Uncoated SiHy contact lenses (i.e., injection molded and extracted with MEK as described in Example 19), PAA coated SiHy contact lenses (made in Example 19) and SiHy contact lenses with a crosslinked coating ( made in examples 14 and 19) are investigated as follows. The PAA coating on PAA coated contact lenses has a surface concentration of carboxy groups of about 62.5 wt. %

where M _COOH denotes the mass of the carboxy group and M _AA denotes the mass of acrylic acid). The crosslinked coating on the contact lenses made in Example 14 is theoretically free of carboxy groups, and the crosslinked coating on the contact lenses made in Example 19 may have a low surface concentration of carboxy groups (should be less than

The lenses are immersed in a dispersion of positively charged particles, after appropriate washing, the particles adhering to the lens are visualized and their number is estimated or counted.

DOWEX ™ 1 × 4 20-50 mesh resins were purchased from Sigma-Aldrich and used as received. DOWEX ™ 1 × 4 20-50 mesh resins are spherical strongly basic anionic Type I resins and are a styrene / divinylbenzene copolymer containing N ⁺ (CH ₃ ) ₃ Cl ^- functionalities and 4% divinylbenzene. Resins 5% 1 × 4 20-50 mesh are dispersed in the PFF and thoroughly mixed by stirring or agitation at about 1000 rpm for 10 seconds. The lenses are immersed in this dispersion and agitated at 1000-1100 rpm for 1 min, then washed with distilled water and agitated for 1 min. The lenses are then placed in water in Petri dishes and images of the lenses are acquired with a Nikon optical microscope with bottom illumination. As shown in FIG. 6, almost the entire surface of the lenses containing the PAA coating is coated with adherent positively charged particles (FIG.6a), while a total of about 50 positively charged particles adhered to the lenses containing the crosslinked coating obtained in Example 19 (FIG.6B) and the positively charged particles did not adhere to the lenses containing the crosslinked coating obtained in Example 14 (FIG. 6C). Few loosely adhering particles may detach from the lens surface and may also be found in the water around the lens.

It should be understood that if larger positively charged particles are used in studies (i.e., DOWEX ™ Monospherical Ion Exchange Resins, crosslinked polystyrene beads, chloride form, size ~ 590 μm, available from Sigma-Aldrich), then the amount of adhered particles can decrease. Approximately 30% of these DOWEX monospherical resins are dispersed in the PBS. The lenses are immersed in this dispersion for ~ 1 min, washed with distilled water. The lenses are then placed in water in Petri dishes and images of the lenses are acquired using a Nikon optical microscope with bottom illumination. It was found that many particles (about 200 particles) adhered to lenses containing a PAA coating, and the particles did not adhere to the lenses on which the crosslinked coating is located. Several commercially available contact lenses have also been investigated. No particles detected on the following lenses: Acuvue® TruEye ™, Acuvue® Advance®, Acuvue® Oasys®, Avaira ™, Biofinity®, Air Optix® and Focus® Night & Day®. Particles are found on the following 4 lens types (in order of increasing particle number): Pure Vision®, 1 Day Acuvue® Moist®, Proclear 1 day, Acuvue® (Etafilcon A) lens. Almost the entire surface of Acuvue® lenses (Etafilcon A) is coated with positively charged particles adhered to.

Negatively charged resins (Amberlite CG50) were purchased from Sigma and used as received. 5% of These Amberlite CG50 granules are dispersed in a PBS and agitated at about 1000 rpm for 10 seconds. Lenses containing a PAA coating are immersed in this dispersion and agitated at 1000-1100 rpm for 1 minute, then rinsed with distilled water and agitated for 1 minute. The lenses are then placed in water in Petri dishes and images of the lenses are acquired using a Nikon optical microscope with bottom illumination. Amberlite particles (negatively charged) are not detectable on lenses containing a PAA coating.

This experiment uses negatively charged beads (Amberlite CG50) that are coated with polyethyleneimine (PEI, positively charged electrolytes). The PEI coating is carried out as follows. PEI (Lupasol SK, 24% in water, Mw ~ 2,000,000) was purchased from BASF and used as received. An aqueous dispersion is prepared containing 1% Amberlite particles and 5% PEI. The pH is adjusted to 7 and the solution is mixed thoroughly (eg by stirring for 30 minutes). The dispersion is then suspended 2-3 times in a large amount of water and filtered 2-3 times, and then the particles are collected (Amberlite coated with PEI). 5% PEI coated Amberlite CG50 Particles are dispersed in a PBS and agitated at about 1000 rpm for 10 seconds. The lenses are immersed in this dispersion and agitated at 1000-1100 rpm for 1 min, then washed with distilled water and agitated for 1 min. The lenses are then placed in water in Petri dishes and images of the lenses are acquired using a Nikon optical microscope with bottom illumination. It was found that many Amberlite particles coated with PEI (positively charged particles due to the presence of PEI) adhered to lenses containing a coating of PAA (example 19). However, there are virtually no PEI coated Amberlite particles adhering to non-SiHy contact lenses (Example 19), SiHy contact lenses that have a crosslinked coating (Example 19), or lenses coated with PAEXPAA (Example 4) ...

Example 31

Sample preparation:

AFM studies were carried out for SiHy contact lenses (made in example 19) in a hydrated state and in a dry state. The lens is removed from the blister pack (sealed and autoclaved) and sectioned off (eg with a safety razor blade). A piece of lens section is fixed vertically in a metal clip as shown in FIG. 7. A small piece of the lens is fixed on top of the holder so that the AFM tip (above the lens section in FIG. 7) can be scanned.

Research using AFM:

Two separate AFM instruments are used to investigate the cross-section of the lens. In both cases (excluding dry samples) AFM scans are performed in phosphate buffered saline (PBS with or without NaCl added, but with an osmolality nearly identical to that of saline) to keep the hydrogel sample fully hydrated.

The first ACM instrument is the Veeco BioScope AFM with a Nanoscope IV controller. Data are collected using triangular silicon cantilevers with a spring constant of 0.58 N / m and a nominal tip radius of curvature of 20-60 nm. Scanning is carried out in constant contact mode (force-volume) with a probe speed equal to 30 μm / s and a force-volume scanning speed equal to 0.19 Hz. Topographic data and force-volume data are accumulated simultaneously. Each force relationship contains approximately 30 data values. During AFM scanning, the lens is completely immersed in the PFF. To ensure a sufficiently high resolution of the force-volume image, a nominal scanning step of no more than 20 μm is used. The force curves of 128 x 28 pixels are accumulated in about 3 hours for each image.

An AFM image of a cross-section of a SiHy contact lens, on which the crosslinked coating (Example 19) is located in a fully hydrated state, is obtained using the force-volume technique and is shown in Fig. 8. In the image, a darker colored area 420 indicates a coating and a lighter colored area 410 indicates a bulky lens material. The average thickness of the crosslinked coating (ie, front and back outer layers) of the SiHy contact lens (Example 19) was found to be about 5.9 μm (standard deviation 0.8 μm) from 7 images, 4 lenses.

где

означает средний модуль поверхности заднего или переднего гидрогелевого слоя и

означает средний модуль поверхности внутреннего слоя), равным примерно 43%.AFM technique allows you to determine the surface modulus (surface softness) at a given position on the lens section. FIG. 9 shows the profile of the surface modulus of the SiHy cross-section of a contact lens on which the crosslinked coating (obtained in Example 19) is in a fully hydrated state. Since the modulus of the material surface is proportional to the deflection of the cantilever, the profile of the modulus of the surface over the section of the contact lens can be obtained by plotting the dependence of deflections of the cantilevers (as a measure of the modulus of the surface of the material in a given position on the section of the lens) on the distance from the side (front or rear surface) of the section along two lines along section shown in FIG. 8. As shown in FIG. 9, the crosslinked coating (front and back outer layers of the contact lens made in Example 19) is softer than the bulk (inner layer) material for a silicone hydrogel lens. When moving along these two lines, the surface modulus initially remains almost constant with an average cantilever deflection of about 52 nm (i.e., the average surface modulus) over the zone from 0 to about 5.9 μm, and then gradually increases in positions located deeper inside the lens, and then reaches a maximum and remains approximately constant (plateau) with an average cantilever deflection of about 91 (i.e., the average surface modulus) over the zone above about 7 μm. The transition from a softer crosslinked coating to a harder bulk material SiHy, which occurs gradually in the range of several micrometers, shows that a gradient of morphology or composition (water content) can be located between the coating surface and the volume of the lens. Surface moduli in the region from 5.9 μm to about 7 μm, i.e. the area near the interface between the outer hydrogel layer and the inner layer of silicone hydrogel material is not used to calculate the average surface modulus. It can be shown by calculation that the front and back hydrogel layers (crosslinked coating) of a SiHy contact lens (example 19) have a reduced surface modulus

where

means the average modulus of the surface of the back or front hydrogel layer and

means the average modulus of the surface of the inner layer), equal to about 43%.

SiHy contact lenses (made in Example 19) were examined using a second AFM instrument. Scanning is performed in Bruker Icon AFM in Quantitative Nanomechanical Measurements (PeakForce QNM) mode using lenses that are fully hydrated (PFF without NaCl, but with glycerol to provide similar osmolality) or dry. The lens section is fixed in a metal clip as described above. The test conditions include the following, the spring constant is 1.3 N / m, the tip radius is 33.3 nm, the sensitivity is 31 nm / V, the scan frequency is 0.4 Hz, and the scan resolution is 512 × 512.

где L_Wet обозначает среднюю толщину наружного гидрогелевого слоя SiHy контактной линзы в полностью гидратированном состоянии и Lory обозначает среднюю толщину этого наружного гидрогелевого слоя SiHy контактной линзы в сухом состоянии) для сшитого покрытия SiHy контактных линз (изготовленных в примере 19) найдено составляющим примерно 277% (для высушенного в сушильном шкафу образца) или примерно 369% (для высушенного в вакууме образца).An AFM cross-sectional image of a SiHy contact lens (Example 19) in a fully hydrated state and in a dry state was obtained using the PeakForce QNM technique. By analyzing the resulting images, the thickness of the crosslinked coating in a fully hydrated state was found to be about 4.4 μm, and the thickness of the crosslinked coating in a dry state was found to be about 1.2 μm for a vacuum-dried sample, about 1.6 μm for an oven-dried sample. sample. Swelling ratio in water

where L _Wet denotes the average thickness of the outer hydrogel layer of a SiHy contact lens in a fully hydrated state and Lory denotes the average thickness of this outer hydrogel layer of a SiHy contact lens in a dry state) for the crosslinked coating of SiHy contact lenses (made in Example 19) found to be about 277% ( for oven-dried sample) or approximately 369% (for vacuum-dried sample).

Example 32

Obtaining compositions for lenses

Composition I is obtained by dissolving a composition of the following composition in 1-propanol: 33 wt. % of the CE-PDMS macromer obtained in example 2, 17 wt. % N- [tris (trimethylsiloxy) -silylpropyl] acrylamide (TRIS-Am), 24 wt. % N, N-dimethylacrylamide (DMA), 0.5 wt. % sodium salt of N- (carbonylmethoxypolyethylene glycol-2000) -1,2-distearoyl-sn-glycero-3-phosphoethanolamine) (L-PEG), 1.0 wt. % Darocur 1173 (DC1173), 0.1 wt. % dye for visible tinting, (5% dispersion of blue pigment, copper phthalocyanine in tris (trimethylsiloxy) silylpropyl methacrylate, TRIS) and 24.5 wt. % 1-propanol.

Composition II is prepared by dissolving in 1-propanol a composition of the following composition: about 32 wt. % of the CE-PDMS macromer obtained in example 2, about 21 wt. % TRIS-Am, about 23 wt. % DMA, about 0.6 wt. % L-PEG, about 1 wt. % DC1173, about 0.1 wt. % dye for visible tinting (5% blue pigment dispersion, copper phthalocyanine in TRIS), about 0.8 wt. % DMPC, about 200 ppm H-tempo and about 22 wt. % 1-propanol.

Lenses making

Lenses are injection molded from the lens composition obtained above in a reusable mold (quartz concave mold half and glass convex mold half) similar to the mold shown in FIG. 1-6 in US Pat. Nos. 7384590 and 7387759 (FIGS. 1-6). The source of UV radiation is a Hamamatsu lamp with a WG335 + TM297 bandpass filter with an intensity of about 4 mW / cm ² . The formulated lens composition is irradiated with UV light for about 25 seconds. Injection molded lenses are extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

PAK primer coating on SiHy contact lenses

A polyacrylic acid coating solution (PAA-1) is prepared by dissolving an amount of PAA (molecular weight: 450 kDa, available from Lubrizol) in a given volume of 1-propanol sufficient to obtain a concentration of about 0.36 wt. %, and the pH value with formic acid is adjusted to about 2.0.

Another PAA coating solution (PAA-2) is prepared by dissolving an amount of PAA (molecular weight: 450 kDa, manufactured by Lubrizol) in a given volume of organic solvent (50/50 1-propanol / H ₂ O) to form a concentration, equal to about 0.39 wt. %, and the pH value with formic acid is adjusted to about 2.0.

The SiHy contact lenses made above were processed using one of the immersion techniques shown in Tables 10 and 11.

PrOH means 100% 1-propanol; PFF means phosphate buffered saline; MEK stands for methyl ethyl ketone; 50/50 means a 50/50 solvent mixture 1-PrOH / H ₂ O.

PrOH means 100% 1-propanol; PFF means phosphate buffered saline; MEK stands for methyl ethyl ketone; 50/50 means a 50/50 solvent mixture 1-PrOH / H ₂ O.

Crosslinked hydrophilic coating

Acrylamide / Acrylic Acid Copolymer Sodium Partial, AAM / AA Copolymer (90/10) (~ 90% solids, AAM / AA copolymer 90/10, Mw 200,000) purchased from Polysciences, Inc. and used as received. PAE (Kymene, according to NMR the content of azetidinium groups is 0.46) is purchased from Ashland in the form of an aqueous solution and used as received. The packaged crosslinking saline is prepared by dissolving about 0.07% w / w. copolymer AAM with AA (90/10) and about 0.15% PAE (initial content of azetidinium groups is about 8.8 mmol) in phosphate buffered saline (PBS) (about 0.044 w / w% NaH ₂ PO ₄ ⋅ H ₂ O, about 0.388 w / w /% Na ₂ HPO ₄ ⋅ 2H ₂ O, about 0.79 w / w% NaCl) and adjusting the pH to 7.2 ~ 7.4. The IPC saline is then heat pretreated for about 4 hours at about 70 ° C. (heat pretreatment). During this heat pretreatment, the copolymer of AAM with AA and PAE partially crosslinks with each other (i.e., all azetidinium groups contained in the PAE are not consumed) to form a water-soluble and thermally crosslinkable hydrophilic polymer material containing azetidinium groups in the branched polymer mesh in NPU saline solution. After thermal pretreatment, the NPU saline is filtered using a 0.22 µm polyethersulfone [PES] membrane filter and cooled to room temperature. Then 10 ppm is added to the finished IPC saline solution. hydrogen peroxide to prevent microflora growth and NPU saline are filtered using a 0.22 µm polyethersulfone [PES] membrane filter.

Lenses containing the PAA primer obtained above are placed in polypropylene lens packs (one lens per section) containing 0.6 ml of NPU saline (half of the saline is added before the lens is placed). The blisters are then sealed with foil and autoclaved for about 30 minutes at about 121 ° C. to provide SiHy contact lenses with crosslinked hydrophilic coatings.

Study of the characteristics of SiHy lenses

Contact lenses made by SiHy with crosslinked hydrophilic coatings and a center thickness of about 0.95 μm have an oxygen permeability (Dk _c or estimated intrinsic Dk) of about 142 to about 150 barrels, a bulk modulus of about 0.72 to about 0.79 MPa, with a water content of about 30% to about 33 wt. %, relative ion permeability of about 6 (compared to the Alsacon lens), and contact angle of about 34 to about 47 °.

Investigation of the characteristics of nanotextured contact lens surfaces

Transmission technique with differential interference contrast (PDIC). Contact lenses are placed on a glass slide and flattened by clamping the lens between the slide and the glass cover slip. Contact lens surfaces are localized and examined by focusing through the lens using a Nikon ME600 microscope with differential interference contrast transmission optics using a 40 × objective. Then, the obtained PDIC images are examined for the presence of surface irregularities (for example, worm-like irregularities located in a random and / or orderly manner, etc.).

Reflection technique with differential interference contrast (ODIC). The lenses are placed on a glass slide and flattened with 4 radial incisions at ~ 90 ° angles. Excess brine is blown off the surface with compressed air. The lens surface was examined with a Nikon Optiphot-2 with differential interference contrast reflectance optics for surface irregularities on contact lens surfaces using 10x, 20x, and 50x objectives. A typical image of each side is captured using a 50 × lens. The contact lens is then inverted, excess saline is removed, and the other side of the contact lens is examined in the same way. Then the obtained images of the ODIC are examined for the presence of surface irregularities (for example, randomly and / or ordered worm-like irregularities, etc.).

Dark-field optical microscopy (TPOM). SST is usually based on darkfield illumination, which is a technique for increasing the contrast of the specimen under test. In this technique, a light source located outside or hidden from the observer's field of view is used to illuminate the sample at an angle with respect to the perpendicular transmitted light. Since unscattered light from the source is not collected by the lens, it is not part of the image and the background of the image appears dark. Since the light source illuminates the sample at a certain angle, the light observed in the sample image is the light scattered by the sample towards the observer, so a contrast is created between this light scattered by the sample and the dark background of the image. This contrast generation mechanism makes darkfield lighting particularly useful for observing scattering phenomena such as haze.

TPOM is used to evaluate contact lens opacity as follows. It is assumed that since the dark field system includes scattered light, dark field data can provide a worst case turbidity estimate. In 8-bit grayscale, each pixel in a digital image is assigned a grayscale intensity (IST) value that ranges from 0-255. Zero represents a pixel that is completely black and 255 represents a pixel that is completely white. Increasing the intensity of the scattered light in the image leads to the formation of pixels with more significant IRT. This SPI value can then be used to quantify the amount of scattered light observed in the dark field image. Haze is characterized by averaging the IST values of all pixels in the area of interest (ISU) (for example, the entire lens or lenticular zone or optical zone of the lens). The experimental setup includes a microscope or equivalent optical device, an attached digital camera, and a dark field stand with a ring light and a variable intensity light source. The optical device is designed / positioned so that the entire contact lens to be examined fills the field of view (usually a field of view of ~ 15 mm (20 mm). The illumination intensity is set so that the desired changes can be observed in the corresponding samples. The illumination intensity is set / calibrated at the same level for each set of samples using a light intensity / scattering standard known to one of ordinary skill in the art For example, a standard consists of two overlapping plastic cover slips (identical and slightly or moderately frosted) Such standards consist of regions with three different averaged IRTs that are includes two areas with intermediate grayscale values and saturated white areas (edges). Dark areas represent an empty dark area. Black and saturated white areas can be used to check the gain and offset (contrast and brightness) settings of the camera. can arr Assign three values to test the linearity of the camera. The intensity of illumination is set such that the average value of the ISU for an empty dark field approaches 0 and that the determined ISU on the digital image at each time instant is the same with an accuracy of ± 5 units of ISU. After calibrating the illumination intensity, the contact lens is immersed in a phosphate-buffered saline filtered through a 0.2 μm sieve in a quartz Petri dish or in a dish of similar transparency, which is placed on a TPOM stand. Then, using calibrated illumination, a digital image of the lens in 8-bit grayscale is taken as seen, and the average value of the ITS for a certain ICU in the portion of the image containing the lens is determined. These operations are repeated for a set of contact lens samples. To ensure consistency, re-calibrate the illumination intensity during the experiment. The turbidity value in the study with SST means the turbidity of the SST, which is

It has been found that SiHy contact lenses, on which a PAA primer coating is obtained using one of the 20-0 and 80-0 immersion techniques, have average SST haze values of about 73%, and have surface irregularities (random worm-like irregularities) that can be visually observed by examining the contact lens in a hydrated state according to the ODIK or PDIK techniques described above. However, surface irregularities have virtually no adverse effect on the light transmission of contact lenses.

It has been found that SiHy contact lenses on which a PAA primer is prepared using one of the 20-1 to 20-4 immersion techniques have small average SST haze values of about 26% (probably due to the presence of pigment particles for visible tinting) and do not have significant surface irregularities (randomly located worm-like irregularities) when investigated using the ODIK or PDIK methods described above.

It has been found that a significant proportion of SiHy contact lenses, on which the PAA primer coating is obtained using the 20-5 immersion technique, has average average values of the turbidity of SSTO, amounting to about 45% and have weakly noticeable surface irregularities when examined by the ODIK or PDIK methods described above. ... However, surface irregularities have virtually no adverse effect on the light transmission of contact lenses.

SiHy contact lenses, on which a PAK primer is prepared using one of the immersion techniques 80-1, 80-2, 80-3, 80-5 and 80-6, do not contain noticeable surface irregularities when examined by the ODIK or PDIK methods described above. However, SiHy contact lenses primed with PAA using one of the 80-0 and 80-4 immersion techniques exhibit noticeable surface irregularities when examined using the ODIC or PDIC techniques described above. However, surface irregularities have virtually no adverse effect on the light transmission of contact lenses.

Example 33

Synthesis of UV absorbing amphiphilic branched copolymer

A 1 L reactor is equipped with a 500 ml dropping funnel, overhead stirrer, reflux condenser with nitrogen / vacuum line adapter, thermometer and sampling adapter. 89.95 g 80% of the partially ethylene functionalized polysiloxane obtained in Example 17A are placed in a reactor and then degassed under vacuum below 1 mbar at room temperature for about 30 minutes. A monomer solution obtained by mixing 1.03 g HEMA, 50.73 g DMA, 2.76 g Norbloc methacrylate, 52.07 g TRIS and 526.05 g ethyl acetate are placed in a 500 ml addition funnel and then degassed under a vacuum of 100 mbar at room temperature for 10 minutes and then flushed with nitrogen. The monomer solution is degassed under the same conditions with two more cycles. The monomer solution is then transferred to a reactor. The reaction mixture is heated to 67 ° C with sufficient stirring. When heated, a solution containing 2.96 g of mercaptoethanol (chain transfer agent, RPC) and 0.72 g of dimethyl-2,2'-azobis (2-methylpropionate) (V-601 is an initiator) and 76.90 g of ethyl acetate are placed into a dropping funnel, then degassed in the same manner as the monomer solution. When the reactor temperature becomes 67 ° C., the initiator / RPC solution is also added to the reactor. The reaction is carried out at 67 ° C for 8 hours. After the completion of the copolymerization, the reactor temperature is reduced to room temperature.

Synthesis of UV absorbing amphiphilic branched prepolymer

The copolymer solution obtained above is functionalized with ethylene to give an amphiphilic branched prepolymer by adding 8.44 g IEM (or 2-isocyanatoethyl methacrylate at the desired molar equivalence ratio) in the presence of 0.50 g DBODL. The mixture is stirred at room temperature in a closed container for 24 hours. The resulting prepolymer is then stabilized with 100 ppm piperonyloxyhydroxytetramethylene, then the solution is concentrated to 200 g (~ 50%) and filtered through 1 μm filter paper. After completion of the reaction, the solvent is replaced with 1-propanol using repeated cycles of evaporation and dilution, the solution is ready for use in the composition. The solids content is determined by removing the solvent in a vacuum oven at 80 ° C.

Obtaining a composition for a lens

Get a composition for the lens having the following composition: 71 wt. % prepolymer obtained above; 4 wt. % DMA; 1 wt. % SRW; 1 wt. % DMPC; 1 wt. % Brij 52 (manufactured by Sigma-Aldrich), and 22 wt. % 1-PrOH.

Lens manufacturing

Lenses are made by injection molding from the lens composition obtained above in a reusable form similar to that shown in FIG. 1-6 in U.S. patents. Nos. 7384590 and 7387759 (Fig. 1-6) using spatially limited UV radiation. The mold includes a concave mold half made of glass and a convex mold half made of quartz. The source of UV radiation is a Hamamatsu lamp with a limited bandwidth up to 380 nm and an intensity of approximately 4.6 mW / cm2. The formulated lens composition is irradiated with UV light for about 30 seconds.

Injection molded lenses are extracted with methyl ethyl ketone (MEK), washed in water, coated with polyacrylic acid by immersing the lenses in a PAA solution in propanol (0.004 wt%, acidified with formic acid to about pH 2.0) and hydrated in water.

NPU saline is prepared from a composition containing about 0.07% PAAm-PAA and a sufficient amount of PAE to provide an initial azetidinium group content of about 8.8 mmol-eq / L (~ 0.15% PAE) by preliminary reaction for 6 hours at about 60 ° C. Then, 5 ppm is added to the NPU saline solutions. hydrogen peroxide to prevent microflora growth and NPU saline solutions are filtered using a 0.22 μm polyethersulfone [PES] membrane filter with 0.22 μm holes. before placing the lens). The blister is then sealed with foil and autoclaved for 30 minutes at 121 ° C.

Study of lens characteristics

The lenses produced have the following characteristics: E '~ 0.82 MPa; DKc ~ 159.4 (using lotrafilcon B as a reference lens, the average thickness in the center is 80 µm and the intrinsic Dk is 110); IP ~ 2.3; water content,% ~ 26.9; and UVA / UVB (UVA / UVB)% T ~ 4.6 / 0.1. When examined with a dark-field microscope, no cracking lines are detected after wiping the lenses. The lenses were found to be very smooth and equivalent to the control lenses as determined by finger rubbing.

Claims (33)

1. A hydrated contact lens having: an outer surface and an opposing rear surface; a layered structural configuration ranging from a front surface to a rear surface, where the layered structural configuration includes a front outer hydrogel layer having a first water content, an inner layer having a second water content, and a rear outer hydrogel layer having a third water content; a water content gradient in a structural configuration from the inner layer to the front or rear outer hydrogel layer in which the first and third water content is greater than the second water content; oxygen permeability of at least 40 bbl / mm; elastic modulus (or Young's modulus) ranging from 0.3 MPa to 1.8 MPa; and an average water contact angle of 80 ° or less and / or a water film disintegration time of at least 10 s, in which the inner layer is a bulk material of a hydrated silicone hydrogel contact lens and consists of a silicone hydrogel material that includes (i) repeating units derived from a silicon-containing vinyl monomer, a silicon-containing vinyl macromer, a silicon-containing prepolymer, or a combination thereof, and (ii) repeating units derived from hydrophilic vinyl monomer, in which each of the front and rear outer hydrogel layers consists of a crosslinked polymeric material that includes (a) poly (ethylene glycol) chains, referred to as PEG chains, which are derived from at least one member selected from the group consisting of PEG- NH ₂ ; PEG-SH; PEG-COOH; H ₂ N-PEG-NH ₂ ; HOOC-PEG-COOH; HS-PEG-SH; H ₂ N-PEG-COOH; HOOC-PEG-SH; H ₂ N-PEG-SH; multi-arm PEG containing one or more amino groups, carboxy groups, or thio groups; A PEG dendrimer containing one or more amino groups, carboxy groups, or thio groups; and combinations thereof, and (b) polymer chains that are derived from a copolymer that is a polymerization product of a composition containing (i) 60 wt% or less of at least one reactive vinyl monomer selected from the group consisting of amino-C ₂ -C ₆ -alkyl (meth) acrylate, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₁₂ -alkyl acrylic acid, N, N-2-acrylamidoglycolic acid, beta-methyl acrylic acid, alpha-phenylacrylic acid, beta-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesoconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene and their combinations; and (ii) at least one non-reactive vinyl monomer selected from the group consisting of acrylamide, methacrylamide, Ν,-dimethylacrylamide, Ν, Ν-dimethylmethacrylamide, N-vinyl pyrrolidone, Ν, Ν-dimethylaminoethyl, N- dimethylaminoethyl acrylate, Ν, Ν-dimethylaminopropyl methacrylamide, Ν, Ν-dimethylaminopropyl acrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, Ν-hydroxyethyl acrylamide, N- [tris (hydroxy-methyl-3-methyl) methyl] -acrylamide pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methyl-2-pyrrolidone, 2-hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, a vinyl monomer fosforilholinsoderzhaschego, C ₁ -C ₄ -alkoksipolietilenglikol (meth) acrylate having an average molecular weight equal to 1500 Yes, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, allyl alcohol, vinyl alcohol, and their combination ation. 2. The hydrated contact lens of claim 1, wherein the anterior and posterior outer hydrogel layers are independently at least 0.1 microns thick. 3. The hydrated contact lens of claim 1, wherein the crosslinked polymeric material of the front and back outer hydrogel layers comprises poly (ethylene glycol) chains, referred to as PEG chains, which are derived from at least one member selected from the group consisting of PEG -NH ₂ ; H ₂ N-PEG-NH ₂ ; H ₂ N-PEG-COOH; multi-arm PEG containing one or more amino groups; A PEG dendrimer containing one or more amino groups; and their combinations. 4. The hydrated contact lens of claim 1, wherein the crosslinked polymeric material of the front and back outer hydrogel layers comprises poly (ethylene glycol) chains, designated PEG chains, which are derived from at least one member selected from the group consisting of PEG-COOH; HOOC-PEG-COOH; multi-arm PEG containing one or more carboxy groups; A PEG dendrimer containing one or more carboxy groups; and their combinations. 5. The hydrated contact lens of claim 1, wherein the crosslinked polymeric material of the front and back outer hydrogel layers comprises poly (ethylene glycol) chains, designated PEG chains, which are derived from at least one member selected from the group consisting of PEG -SH; HS-PEG-SH; HOOC-PEG-SH; H ₂ N-PEG-SH; multibeam PEG containing one or more thio groups; A PEG dendrimer containing one or more thio groups; and their combinations. 6. The hydrated contact lens of claim 1, wherein the crosslinked polymeric material of the front and rear outer hydrogel layers comprises polymer chains that are derived from a copolymer that is a polymerization product of a composition containing (i) 60 wt% or less of at least one reactive vinyl monomer, and (ii) said at least one non-reactive vinyl monomer selected from the group consisting of acrylamide, methacrylamide, Ν,-dimethylacrylamide, Ν,-dimethylmethacrylamide, Ν,-dimethylaminopropyl,,-dimethylaminopropyl dimethylaminopropylacrylamide, and combinations thereof, wherein said at least one reactive vinyl monomer is selected from the group consisting of amino-C ₂ -C ₆ -alkyl (meth) acrylate, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ - alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid, C ₁ - C ₁₂ -alkylacrylic acid, Ν, Ν-2- acrylamidoglycolic acid, beta-methyl acrylic acid, and combinations thereof. 7. A hydrated contact lens according to claim 1, wherein the crosslinked polymeric material of the front and rear outer hydrogel layers comprises polymer chains that are derived from a copolymer that is a polymerization product of a composition containing (i) 60% by weight or less of said at least a reactive vinyl monomer, and (ii) said at least one non-reactive vinyl monomer is selected from the group consisting of Ν, Ν-dimethylaminoethyl, Ν, Ν-dimethylaminoethyl acrylate, C ₁ -C ₄ -alkoksipolietilenglikol (meth) acrylate having a weight average molecular weight equal to 1500 Da, and combinations thereof, in which the specified at least one reactive vinyl monomer is selected from the group consisting of amino-C ₂ -C ₆ -alkyl (meth) acrylate, C ₁ -C ₆ -alkylamino C ₂ -C ₆ -alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₁₂ -alkyl acrylic acid, N, N-2-acrylamidoglycolic acid, beta-methyl acrylic acid, and combinations thereof. 8. The hydrated contact lens of claim 1, wherein the crosslinked polymeric material of the front and rear outer hydrogel layers comprises polymer chains that are derived from a copolymer that is a polymerization product of a composition comprising (i) 60 wt% or less of at least one reactive vinyl monomer, and (ii) said at least one non-reactive vinyl monomer selected from the group consisting of glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N- [tris (hydroxymethyl) methyl] -acrylamide 2-hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, allyl alcohol, vinyl alcohol, and combinations thereof, wherein said at least one reactive vinyl monomer is selected from the group consisting of amino-C ₂ -C ₆ -alkyl ( meth) acrylate, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino C ₂ -C ₆ -alkyl (meth) acryl mid, acrylic acid, C ₁ -C ₁₂ -alkyl acrylic acid, Ν, Ν-2-acrylamidoglycolic acid, beta-methyl acrylic acid, and combinations thereof. 9. The hydrated contact lens of claim 1, wherein the crosslinked polymeric material of the front and rear outer hydrogel layers comprises polymer chains that are derived from a copolymer that is a polymerization product of a composition containing (i) 60 wt% or less of at least one reactive vinyl monomer, and (ii) said at least one non-reactive vinyl monomer selected from the group consisting of N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1- methyl 5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, N-vinylpyrrolidone, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, and combinations thereof, wherein said at least one reactive vinyl monomer is selected from the group consisting of amino-C ₂ -C ₆ -alkyl ( meth) acrylate, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylate, allylamine, vinylamine , amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₁₂ -alkyl acrylic acid, Ν, Ν -2-acrylamidoglycolic acid, beta-methyl acrylic acid, and combinations thereof. 10. A hydrated contact lens according to claim 1, wherein the crosslinked polymeric material of the front and rear outer hydrogel layers comprises polymer chains that are derived from a copolymer that is a polymerization product of a composition containing (i) 60 wt% or less of at least one reactive vinyl monomer, and (ii) said at least one non-reactive vinyl monomer that is a phosphorylcholine-containing vinyl monomer, wherein said at least one reactive vinyl monomer is selected from the group consisting of amino-C ₂ -C ₆ -alkyl (meth) acrylate, C ₁ -C ₆ -alkylamino-C ₂ -C ₆ -alkyl (meth) acrylate, allylamine, vinylamine, amino-C ₂ -C ₆ -alkyl (meth) acrylamide, C ₁ -C ₆ -alkylamino -C ₂ -C ₆ -alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₁₂ -alkyl acrylic acid, Ν, Ν-2-acrylamidoglycolic acid, beta-methyl acrylic acid, and combinations thereof. 11. The hydrated contact lens of claim 1, wherein the hydrated contact lens has: an oxygen permeability of at least 60 bbl / mm and / or an average water contact angle of 70 ° or less. 12. The hydrated contact lens of claim 1, wherein the hydrated contact lens has: an oxygen permeability of at least 80 bbl / mm and / or an average water contact angle of 60 ° or less. 13. The hydrated contact lens of claim 1, wherein the hydrated contact lens has: an oxygen permeability of at least 100 bbl / mm and / or an average water contact angle of 50 ° or less. 14. The hydrated contact lens of claim 1, wherein the hydrated contact lens has a water film disintegration time of at least 10 seconds. 15. The hydrated contact lens of claim 1, wherein the first and third water content is greater than 75% by weight. 16. The hydrated contact lens of claim 1, wherein the first and third water content is at least 1.3 times the second water content. 17. The hydrated contact lens of claim 1, wherein the first and third water content is at least 1.4 times the second water content. 18. The hydrated contact lens of claim 1, wherein the first and third water content is at least 1.5 times the second water content. 19. A hydrated contact lens according to any one of paragraphs. 1-18, in which the silicone hydrogel material comprises repeating units derived from a polysiloxane vinyl monomer, a polysiloxane vinyl macromer, or combinations thereof. 20. A hydrated contact lens according to claim 19, wherein the polysiloxane vinyl monomer or macromer are monomethacrylated or monoacrylated polydimethylsiloxanes, vinyl carbonate end-group polydimethylsiloxanes, vinyl carbamate end-group polydimethylsiloxy-concevyl group of polydimethylsiloxanes containing acrylate end group polydimethylsiloxanes containing methacrylate end group polydimethylsiloxanes, bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane, N, N, N ', N'-tetrakis (3-hydroxypropyloxy-2-alpha) -bis-3-aminopropyl-polydimethylsiloxane; polysiloxanylalkyl (meth) acrylic monomer or the reaction product of glycidyl methacrylate with an amino group-containing polydimethylsiloxane. 21. The hydrated contact lens of claim 19, wherein the silicone hydrogel material comprises repeating units derived from a hydrophilic vinyl monomer selected from the group consisting of Ν, Ν-dimethylacrylamide, Ν, Ν-dimethylmethacrylamide, 2-acrylamidoglycolic acid, 3- acryloylamino-1-propanol, N-gidroksietilakrilamida, Ν- [tris (hydroxymethyl) methyl] acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, trimethylammonium 2-gidroksipropilmetakrilatgidrohlorida, aminopropilmetakrilatgidrohlorida, dimethylaminoethyl glitserinmetakrilata, allyl alcohol, C ₁ -C ₄ -alkoxypolyethylene glycol (meth) acrylate having a weight-average molecular weight of up to 1500, methacrylic acid, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl- 5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl- 3-methylene-2-pi rrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene- 2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylformamide, N-vinylacetamide, Ν-vinylisopropylamide, N-vinyl-N-methylacetamide, N- vinylcaprolactam and mixtures thereof. 22. The hydrated contact lens according to claim. 21 wherein the silicone hydrogel material further comprises repeating units derived from a crosslinking agent selected from the group consisting of tetraetilenglikoldiakrilata, trietilenglikoldiakrilata, etilenglikoldiatsilata, diethylene glycol, tetraetilenglikoldimetakrilata, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, pentaeritrittetrametakrilata , bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine diamine dimethyl acrylamide, ethylene diamine diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3-bis (methacrylamidopropyl) -1,3-bis (methacrylamidopropyl) -1,3-bis (methacrylamidopropyl) -1 , Ν, Ν'-methylenebismethacrylamide, Ν, Ν'-ethylenebisacrylamide, N, N'-ethylenebismethacrylamide, 1,3-bis (N-methacrylamidopropyl) -1,1,3,3-tetrakis- (trimethylsiloxy) disiloxane, 1, 3-bis (methacrylamidobutyl) -1,1,3,3 -tetrakis (trimethylsiloxy) -disiloxane, 1,3-bis (acrylamidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacryloxyethylureidopropyl) -1,1,3,3-tetrakis ( trimethylsiloxy) disiloxane, and combinations thereof. 23. A hydrated contact lens according to any one of paragraphs. 1-18, in which the silicone hydrogel material comprises repeating units derived from a hydrophilic vinyl monomer selected from the group consisting of, Ν-dimethylacrylamide, Ν,-dimethylmethacrylamide, 2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, Ν-gidroksietilakrilamida, N- [tris (hydroxymethyl) methyl] acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, trimethylammonium 2-gidroksipropilmetakrilatgidrohlorida, aminopropilmetakrilatgidrohlorida, dimethylaminoethyl glitserinmetakrilata, allyl alcohol, C ₁ -C ₄ -alkoksipolietilenglikol ( meth) acrylate having a weight-average molecular weight of up to 1500, methacrylic acid, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2- pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2- pyrrolidone, 1-n-propyl-5-methylene-2-pyrrole don, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene- 2-pyrrolidone, N-vinyl-2-pyrrolidone, vinylpyridine, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, N-vinylcaprolactam, and mixtures thereof. 24. A hydrated contact lens according to any one of paragraphs. 1-18, wherein the silicone hydrogel material further comprises repeating units derived from a crosslinking agent selected from the group consisting of tetraetilenglikoldiakrilata, trietilenglikoldiakrilata, etilenglikoldiatsilata, diethylene glycol, tetraetilenglikoldimetakrilata, triethylene glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, pentaeritrittetrametakrilata, bisphenol A dimethacrylate, vinyl methacrylate , ethylenediamine-dimethylacrylamide, ethylenediamine-diacrylamide, glycerol-dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, allyl methacrylate, 1,3-bis (methacrylamidopropyl) -1,1,3,3-tetrakis (trimethyl-silane-methyloxy-) disyl methylenebismethacrylamide, Ν, Ν'-ethylenebisacrylamide, N, N'-ethylenebismethacrylamide, 1,3-bis (N-methacrylamidopropyl) -1,1,3,3-tetrakis- (trimethylsiloxy) disiloxane, 1,3-bis (methacrylamidobutyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1 , 3-bis (acrylamidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacryloxyethylureidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, and combinations thereof. 25. A hydrated contact lens according to any one of paragraphs. 1-18, in which the silicone hydrogel material comprises repeating units derived from a silicon-containing vinyl monomer selected from the group consisting of N- [tris (trimethylsiloxy) silylpropyl] - (meth) acrylamide, N- [tris (dimethylpropylsiloxy) - silylpropyl] - (meth) acrylamide, Ν- [tris (dimethylphenylsiloxy) silylpropyl] (meth) acrylamide, Ν- [tris (dimethylethylsiloxy) silylpropyl] (meth) acrylamide, N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) -2-methylacrylamide; N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) acrylamide; Ν, Ν-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] -2-methylacrylamide; Ν, Ν-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] acrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) -2-methylacrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) acrylamide; N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] -2-methylacrylamide; Ν, Ν-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] acrylamide; N- [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] -2-methylacrylamide; N- [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] acrylamide; Ν, Ν-bis [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] -2-methylacrylamide; Ν, Ν-bis [2-hydroxy-3- (3- (tert-butyldimethylsilyl) propyloxy) propyl] acrylamide; 3-methacryloxypropylpentamethyldisiloxane, tris (trimethylsilyloxy) silylpropylmethacrylate, (3-methacryloxy-2-hydroxypropyloxy) propylbis (trimethylsiloxy) methylsilane), (3-methacryloxy-2-hydroxypropyloxy) propyltris (trimethylsilyloxy-3 hydroxyethoxy) -propyloxy) propylbis (trimethylsiloxy) methylsilane, N-2-methacryloxyethyl-O- (methylbis-trimethylsiloxy-3-propyl) silyl carbamate, 3- (trimethylsilyl) propylvinylcarbonate, 3- (vinyloxycarbonylrisiloxy) trimethio) [tris (trimethylsiloxy) silyl] propylvinyl carbamate, 3- [tris (trimethylsiloxy) silyl] propyl allyl carbamate, 3- [tris (trimethylsiloxy) silyl] propyl vinyl carbonate, tert-butyldimethylsiloxyethyl vinyl carbonate, trimethyl vinyl carbonate and trimethyl vinyl carbonate, trimethyl vinyl carbonate, and trimethyl vinyl carbonate

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