Silicone-containing prepolymers with hydrophilic polymeric chains

(54) Title: PREPOLÍMEROS CONTAINING SILICONE (57) Abstract:

WITH HYDROPHILE POLYMERIC CHAINS

PENDING (30) Unionist Priority: 22/03/2007 us 60 / 896,326 (73) Holder (s): Novartis AG (72) Inventor (s): Arturo Morberto Medina, Frank Chang, Jian S. Zhou, Robert Scott (74 ) Attorney (s): Dannemann, Siemsen, Bigler & Ipanema Moreira (86) International Request: pct US2008057775 of 3/21/2008 (87) International Publication: wo 2oos / n6i32de 25/09/2008

Descriptive Report of the Invention Patent for PREPOLYMERS CONTAINING SILICON WITH HANGING POLYMERIC CHAINS PENDING.

The present invention relates to a class of prepolymers containing silicone and uses thereof. Specifically, the present invention relates to silicone hydrogel contact lenses manufactured from this class of silicone-containing prepolymers.

Background

Recently, flexible silicone hydrogel contact lenses have become popular because of their high oxygen permeability and comfort. Flexible contact lenses can conform closely to the shape of the eyes, so oxygen can easily envelop the lenses. Flexible contact lenses must allow oxygen from the surrounding air (ie oxygen) to reach the cornea because it does not receive oxygen from the blood supply like other tissues. If enough oxygen does not reach the cornea, it will swell. Extended periods of oxygen deprivation cause unwanted growth of blood vessels in the cornea. When high oxygen permeability is achieved, silicone hydrogel contact lenses allow sufficient oxygen to permeate through the lens towards the cornea, which produces minimal adverse effects on the health of the cornea.

However, all commercially available silicone hydrogel contact lenses are produced according to a conventional casting molding technique, involving the use of disposable plastic molds and a mixture of monomers and / or macromers. There are numerous disadvantages to the conventional casting molding technique. For example, a traditional die-casting manufacturing process should include lens extraction, where unpolymerized monomers must be removed from the lens using an organic solvent. Such extraction of the lenses increases the production cost and decreases the production efficiency. In addition, disposable plastic molds inherently have unavoidable dimensional variations, since during injection molding of plastic molds, fluctuations in the dimensions of the molds can occur as a result of fluctuations in the production process (temperatures, pressures, material properties) and also because of the resulting molds, which may undergo non-uniform contraction after injection molding. These dimensional changes in the mold can lead to fluctuations in the parameters of the contact lenses to be produced (maximum refractive index, diameter, basic curve, central thickness, etc.) and to a low fidelity in the duplication design of complex lenses.

The disadvantages described above and found in a conventional casting molding technique can be overcome by employing the so-called Lightstream Technology® (CIBA Vision), which involves (1) a lens-forming composition that is substantially free from monomers and comprising a prepolymer substantially purified with ethylenically unsaturated groups, (2) reusable molds produced with high precision and (3) curing under spatial limitation of actinic radiation (for example, UV), as described in US Patent Nos. 5,508,317, 5,583,463, 5,789,464 and 5,849,810. The lenses can be produced at a relatively low cost according to Lightstream Technology® and in order to have high fidelity to the original design of the lenses.

In order to make full use of Lightstream Technology® for the manufacture of silicone hydrogel contact lenses, there is still a need for new actinically crosslinkable prepolymers, suitable for the manufacture of silicone hydrogel contact lenses with desired volume and surface properties in accordance with with Lightstream Technology®.

Summary of the Invention

The present invention, in one aspect, provides an actinically crosslinkable prepolymer. The prepolymer of the invention comprises: in the copolymer chain of the prepolymer, (1) siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers: (2) hydrophilic units derived from one or more hydrophilic and / or monomers one or more hydrophilic macromers; and (3) pendant hydrophilic polymer chains that are covalently attached to the copolymeric chain and derived from at least one preformed hydrophilic polymer having a single crosslinkable group, wherein the pendant hydrophilic chains are free from actinically crosslinkable groups, wherein the hydrophilic polymer preform has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer, but high enough to provide a silicone hydrogel contact lens, which is obtained from the prepolymer, with an angle of contact with water of about 90 degrees or less, without surface post-curing treatment, when present in the prepolymer in an amount of about 2% to about 30% by weight, wherein the prepolymer is capable of being actinically crosslinked, in the absence of one or more monomers, to form the silicone hydrogel contact lenses.

In another aspect, the invention provides a flexible contact lens. The flexible contact lens of the invention comprises: a silicone hydrogel material that is obtained by curing a lens forming material in a mold, wherein the lens forming material comprises an actinically crosslinkable or polymerizable prepolymer, wherein the prepolymer comprises (1) siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers; (2) hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; and (3) pendant hydrophilic polymer chains that are covalently attached to the copolymeric chain and derived from one or more preformed hydrophilic polymers, each having a single crosslinkable group, wherein the pendant hydrophilic chains are free from actinically crosslinkable groups, where the preformed hydrophilic polymer has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer, but high enough to provide the flexible contact lens with a water contact angle of about 90 degrees or less, without surface post-curing treatment, when it is present in the prepolymer in an amount of about 2% about 30% by weight.

In a further aspect, the invention provides a method for producing flexible contact lenses. The method comprises the steps of: provision of a mold for manufacturing a flexible contact lens, wherein the mold has a first mold half with a first molding surface defining the front surface of a contact lens and a second mold half with a second mold surface defining the rear surface of the contact lens, where the first and second mold halves are configured to receive each other, such that a cavity is formed between said first and second mold surfaces; introducing the lens forming material into the cavity, wherein the lens forming material comprises one or more actinically crosslinkable prepolymers and is substantially free of vinyl monomer and / or crosslinking agent, each of which one or more prepolymers comprises ( 1) siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers; (2) hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; and (3) hydrophilic polymeric pendant chains that are covalently attached to the copolymeric chain and derived from one or more preformed hydrophilic polymers, each having a single crosslinkable group, wherein the pendant hydrophilic chains are free from actinically crosslinkable groups, where the preformed hydrophilic polymer has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer, but high enough to provide the flexible contact lens with a water contact angle of about 90 degrees or less, without surface post-curing treatment, when it is present in the prepolymer in an amount of about 2% about 30% by weight; and actinically irradiating the composition in the mold to crosslink said one or more crosslinkable prepolymers to form the contact lens.

Detailed Description of Embodiments of the Invention

Unless otherwise defined, all technical and scientific terms used in this document have the same meaning commonly understood by one skilled in the art to which this invention belongs. Generally, the nomenclature used in this document and laboratory procedures are well known and generally employed in the art. Conventional methods are used for these procedures, such as those provided in the art and in various generic references. When the term is provided in the singular, the inventors also contemplate the plural of that term. The nomenclature used in this document and the laboratory procedures described are those well known and generally employed in the art.

An ophthalmic device as used in this document refers to a contact lens (rigid or flexible), intraocular lenses, a corneal layer, other ophthalmic devices (for example, stents, glaucoma shunt or similar) used on or around eyes or ocular neighborhood.

Contact lens refers to a structure that can be placed over a user's eyes. A contact lens can correct, improve or change the user's vision, but that need is not the case. A contact lens can be of any suitable material known in the art or developed later, it can be a flexible lens, a rigid lens, or a hybrid lens. A silicone hydrogel contact lens refers to a contact lens comprising a silicone hydrogel material.

A hydrogel or hydrogel material refers to a polymeric material that can absorb at least 10% by weight of water when it is fully hydrated.

A silicone hydrogel refers to a silicone-containing hydrogel obtained by copolymerizing a polymerizable composition comprising at least one silicone-containing monomer or at least one silicone-containing macromer or at least one crosslinkable silicone-containing prepolymer.

Hydrophilic as used in this document describes a material or portion of it that will readily associate with water rather than lipids.

A monomer means a low molecular weight compound that can be polymerized. Low molecular weight typically means average molecular weights less than 700 Daltons.

An actinically polymerizable monomer '¹ refers to a monomer that can be actinically polymerized. According to the invention, an actinically polymerizable monomer can be a vinyl monomer or a compound comprising two thiol groups. A compound with two thiol groups can participate in the polymerization of the growth radical in thiol-ene stages with a monomer with vinyl group to form a polymer. The growth radical polymerization in stages can be used in the manufacture of contact lenses, as described in jointly owned US Patent Application Number 60 / 869,812, filed December 13, 2006 (titled PRODUCTION OF OPHTHALMIC DEVICES BASED ON PHOTO -INDUCED STEP GROWTH POLYMERIZATION, incorporated herein by reference, in its entirety.

A siloxane-containing monomer refers to a Ri

-Si-omonomer containing a divalent radical of R₂ⁿ where Ri and R₂ they are independently a monovalent C1-C10 alkyl, C1-C10 ether, C1-C10 fluoralkyl, C1-C10 fluorether or C6-Cig aryl radical, which may comprise hydroxy group, primary, secondary or tertiary amine, carboxy group or carboxylic acid; n is an integer of 4 or more.

A vinyl monomer, as used herein, refers to a monomer that has an ethylenically unsaturated group and can be actinically or thermally polymerized.

The term olefinically unsaturated group or ethylenically unsaturated group is used in this document in a broad sense and is intended to encompass any groups containing a group> C = C <. Exemplary ethylenically unsaturated groups include, without limitation, acryloyl, methacryloyl, allyl, vinyl, styrenyl or other groups containing C = C.

As used in this document actinically with reference to curing, crosslinking or polymerizing a polymerizable composition, a prepolymer or material means that curing (for example, cross-linked and / or polymerized) is carried out by actinic irradiation, such as, for example, UV irradiation, ionized radiation (eg gamma or x-ray irradiation, microwave irradiation and the like). Methods of thermal curing or actinic curing are well known to those skilled in the art.

The term fluid as used in this document indicates that a material is capable of flowing as a liquid.

A hydrophilic monomer refers to a monomer that can be polymerized to form a polymer that is soluble in water or can absorb at least 10% by weight of water.

A hydrophobic monomer, as described herein, refers to a vinyl monomer that is polymerized to form a polymer that is insoluble in water and can absorb less than 10% by weight of water.

A macromer refers to a compound of medium and high molecular weight that can be polymerized and / or cross-linked. Average and high molecular weight typically means average molecular weights greater than 700 Daltons.

An actinically polymerizable macromer refers to a macromer that can be actinically polymerized. According to the invention, an actinically polymerizable macromer can be a macromer with one or more ethylenically unsaturated groups or with two or more thiol groups, which can participate both in the growth polymerization of the free radical chain and in the growth radical polymerization in thiol-ene steps. Preferably, a macromer contains ethylenically unsaturated groups and can be actinically or thermally polymerized.

A prepolymer refers to a starting polymer which contains several actinically crosslinkable groups and can be actinically cured (for example, crosslinked) in order to obtain a crosslinked polymer having a molecular weight much greater than that of the starting polymer.

Actinically crosslinkable groups refers to ethylenically unsaturated groups or thiol groups.

A silicone-containing prepolymer refers to a silicone-containing prepolymer and can be actinically cross-linked to obtain a cross-linked polymer having a molecular weight much greater than that of the starting polymer.

Molecular weight of a material (including monomeric or macromeric materials), as used in this document, refers to the numerical average molecular weight, unless otherwise specifically noted or unless the test conditions indicate otherwise.

Polymer means a polymeric material formed by the polymerization of one or more monomers.

As used herein, the term actinically functionalizes with reference to a copolymer or compound is intended to describe that one or more actinically crosslinkable groups have been covalently attached to a copolymer or compound through the pendant or terminal functional groups of the copolymer or compound according to a coupling process.

As used herein, the term multiple refers to at least two, preferably at least three.

As used herein, a preformed, crosslinkable hydrophilic polymer refers to a hydrophilic polymer that contains one or more crosslinkable groups and is prepared or obtained before being added to a reaction mixture for the manufacture of a prepolymer of the invention.

The term pending hydrophilic polymer chains with reference to a prepolymer of the invention is intended to describe that the prepolymer comprises hydrophilic polymer chains, where each is anchored to the main chain of the prepolymer through a simple covalent bond (preferably at one end of the hydrophilic polymer chain) .

A photoinitiator refers to a chemical that initiates a crosslinking / polymerization reaction using light. Suitable photoinitiators include, without limitation, methyl benzoyl ether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone, types Darocure® and types Irgacure®, preferably Darocure® 1173, and Irgacure® 2959.

A thermal initiator refers to a chemical substance that initiates the crosslinking / polymerization reaction of the radical using thermal energy. Examples of suitable thermal initiators include, but are not limited to, 2,2-azobis (2,4-dimethylpentanonitrile), 2,2-azobis (2-methylpropanonitrile), 2,2'-azobis (2-methylbutanonitrile), peroxides, such as , benzoyl peroxide and the like Preferably, the thermal initiator is 2,2'azobis (isobutyronitrile) (AIBN).

A spatial limitation of actinic radiation refers to an act or process in which the radiation of energy in the form of rays is directed, for example, by a mask or screen or combinations of them, being imposed, in a spatially restricted way, on a area having a well-defined peripheral boundary. For example, a spatial limitation of UV radiation can be achieved by using a mask or screen and that has a transparent or open region (region without a mask) surrounded by a region impervious to UV (masked region), as illustrated schematically in figures 1 -9 of US Patent number 6,627,124 (incorporated herein in its entirety by reference). The maskless region has a well-defined peripheral boundary with the maskless region. The energy used for the crosslinking is radiation energy, especially UV radiation, gamma radiation, electron radiation or thermal radiation, the radiation energy being preferably in the form of a substantially parallel beam, in order, on the one hand, to obtain good restriction and on the other hand, efficient use of energy.

Visibility tinting with reference to the lens means staining (or coloring) a lens to allow the user to easily locate the lens in a clear solution within the lens case, disinfection or cleaning container. It is well known in the art that a dye and / or pigment can be used in the dye for visibility of a lens.

Dye means a substance that is soluble in a solvent and that is used to provide color. Dyes are typically translucent and absorb, but do not diffuse light. Any suitable biocompatible dye can be used in the present invention.

A pigment means a powdered substance that is suspended in a liquid in which it is insoluble. A pigment can be a fluorescent pigment, phosphorescent pigment, pearl pigment or conventional pigment. Although any suitable pigment can be employed, it is presently preferred that the pigment is heat resistant, non-toxic and insoluble in aqueous solutions.

Surface modification as used in this document, means that an article was treated in a surface treatment process (or a surface modification process) before or after the formation of the article, in which (1) a coating is applied to the surface of the article, (2) chemical species are absorbed on the surface of the article, (3) the chemical nature (for example, electrostatic charge) of the chemical groups on the surface of the article are altered or (4) the surface properties of the article are otherwise modified. Exemplary surface treatment processes include, but are not limited to, plasma processes, in which an ionized gas is applied to the surface of an article (see, for example, US Patent numbers 4,312,575 and 4,632,844 incorporated herein in its entirety as a reference); a surface treatment with energy other than plasma (for example, a static electrical charge, irradiation or other source of energy); chemical treatments; the graft of hydrophilic monomers or macromers on the surface of an article; mold transfer coating process described in US Patent No. 6,719,929 (incorporated herein in its entirety by reference); the incorporation of wetting agents into the lens formulation for the manufacture of contact lenses (ie, surface treatment prior to polymerization) proposed in US Patent Numbers 4,045,547, 4,042,552, 5,198,477, 5,219,965, 6,367,929 and 6,822,016, 7,279,507 (incorporated in this document in its entirety as a reference); reinforced mold transfer coating described in PCT Patent Application Publication WO2007 / 146137 (incorporated herein in its entirety by reference); and layered coating (LbL coating) obtained according to the methods described in US Patent Serial Number 6,451,871, 6,719,929, 6,793,973, 6,811,805, 6,896,926 (incorporated herein by reference in its entirety).

Exemplary plasma gases and processing conditions are described in US Patent numbers 4,312,575 and 4,632,844. Plasma gas is preferably a mixture of low alkanes and nitrogen, oxygen and an inert gas.

LbL coating, as used in this document, refers to a coating that is not covalently attached to a contact lens or half of the mold and is obtained through a layer-by-layer (LbL) deposition of polyionic materials (or loaded) and / or unloaded on the lens or half of the mold. An LbL coating can be composed of one or more layers.

As used in this document, a polyionic material refers to a polymeric material that has several charged groups or ionizable groups, such as, polyelectrolytes, doped conducting polymers of the p and n type. Polyionic materials include both polycationic (having positive charges) and polyanionic (having negative charges) materials

The formation of an LbL coating on a contact lens or half of the mold can be accomplished in several ways, for example, as described in US Patent Serial Numbers 6,451,871, 6,719,929, 6,793,973, 6,811,805, 6,896,926 (incorporated in this document in its entirety as a reference).

Post-cure surface treatment, with reference to a silicone hydrogel material or a flexible contact lens, means a surface treatment process that is carried out after the formation (curing) of the hydrogel material or flexible contact lens in a mold.

A hydrophilic surface with reference to a silicone hydrogel material or contact lens means that the silicone hydrogel material or contact lens has surface hydrophilicity characterized by having a weighted contact angle of water of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, more preferably about 60 degrees or less.

An average contact angle refers to an angle of contact with water (lead angle measured by the Wilhelmy Plate method), which is obtained by weighted measurements from at least 3 individual contact lenses.

An antimicrobial agent, as used herein, refers to a chemical substance that is able to slow or eliminate the growth of microorganisms, such that the term is known in the art.

Antimicrobial metals ”are metals whose ions have an antimicrobial effect and which are biocompatible. Preferred antimicrobial metals include Ag, Au, Pt, Pd, Ir, Sn, Cu, Sb, Bi and Zn, with Ag being most preferred.

Nanoparticles containing antimicrobial metal refers to particles having a size less than 1 micrometer and containing at least one antimicrobial metal present in one or more of its oxidation states.

Antimicrobial metal nanoparticles refers to particles that are made essentially of an antimicrobial metal and are less than 1 micrometer in size. The antimicrobial metal in the antimicrobial metal nanoparticles may be present in one or more of its oxidation states. For example, nanoparticles containing silver may contain silver in one or more of its oxidation states, such as,

Ag °, Ag¹⁺and Ag²⁺.

Stabilized antimicrobial metal nanoparticles refer to antimicrobial metal nanoparticles that are stabilized by a stabilizer during preparation. The stabilized antimicrobial metal nanoparticles can be either positively or negatively charged or neutral, depending largely on a material (or so-called stabilizer) that is present in a solution for preparing the nanoparticles and can stabilize the resulting nanoparticles. A stabilizer can be any suitable known material. Exemplary stabilizers include, without limitation, positively charged polyionic materials, negatively charged polyionic materials, polymers, surfactants, salicylic acid, alcohols and the like.

The oxygen carrying capacity of a lens, as used in this document, is the rate at which oxygen will pass through a specific ophthalmic lens. The oxygen transmission capacity, Dk / t, is conventionally expressed in units of barrers / mm, where t is the average thickness of the material [in units of mm] with respect to the area being measured and barrer / mm is defined as:

[(cm³ oxygen) / (cm² ) (second) (mm Hg)] x 10 '⁹

The intrinsic oxygen permeability, Dk, of a lens material does not depend on the thickness of the lens. Intrinsic oxygen permeability is the reason that oxygen will pass through a material. Oxygen permeability is conventionally expressed in units of barrers, where barrer is defined as:

[(cm³ oxygen) (mm) / (cm² ) (seconds) (mm Hg)] x 10 '¹⁰

These are the units generally employed in the art. Thus, in order to be consistent with employment in the technique, the barrer unit will have the meanings defined above. For example, a lens with a Dk of 90 barrers (oxygen permeability barrels) and a thickness of 90 microns (0.090 mm) would have a Dk / t of 100 barrers / mm (barrers / mm of oxygen transmission capacity). According to the invention, a high oxygen permeability with reference to a material or a contact lens characterized by apparent oxygen permeability of at least 40 barrers or more, measured with a sample (film or lens) of 100 microns in thickness of according to a coloumetric method described in the examples.

Ion permeability through a lens correlates to both the lonoflow diffusion coefficient and the lonoton ion permeability coefficient.

The diffusion coefficient of lonoflux, D, is determined by applying Fick's law as follows:

D = - n '/ (A x dc / dx) where n' = ion transport rate [mol / minute]

A = exposed area of ​​the lens [mm²]

D = Lonoflux diffusion coefficient [mm²/ minute] dc = difference in concentration [mol / L] dx = lens thickness [mm]

The permeability coefficient of the lonoton ion, P, is then determined according to the following equation:

ln (1 - 2C (t) / C (0)) = -2APt / Vd where: C (t) = concentration of sodium ions at time t in the receiving cell

C (0) = initial sodium ion concentration in the donor cell

A = membrane area, that is, area of ​​the lens exposed to cells

V = cell compartment volume (3.0 mL) d = average lens thickness in the exposed area

P = coefficient of permeability

A diffusion coefficient of lonoflux, D, greater than about

1.5 x 10 '⁶ mm²/ minutes is preferred, although more than about 2.6 x 10 '⁶mm²/ minutes is more preferred and more than about 6.4 x 10 '⁶ mm²/ minutes is most preferred.

It is known that the movement of the lens in the eye is necessary to ensure good tear exchange and ultimately, to ensure the health of the cornea.

The permeability of the ion is one of the predictors of movement in the eye, due to the permeability of the ions is believed to be directly proportional to the permeability of water.

In general, the invention relates to a class of prepolymers containing actinically crosslinkable silicone with pendent hydrophilic polymer chains. Such prepolymers can be used to prepare silicone hydrogel contact lenses, specifically according to Lightstream Technology® (CIBA Vision). It is known that a silicone hydrogel material typically has a surface of at least some areas of its surface, which is hydrophobic (non-wetting). Hydrophobic surface or surface areas will absorb lipids or proteins from the eye environment and may adhere to the eyes. Thus, a silicone hydrogel contact lens will generally require a surface modification that is typically performed after fusing molding the lens.

However, a prepolymer of the invention can be used to prepare silicone hydrogel contact lenses with a high oxygen permeability and a hydrophilic surface without surface post cure treatment. It is believed that when a solution of a prepolymer of the invention is introduced into a mold for making contact lenses, the hydrophilic polymer chains dangling from the prepolymer are preferably absorbed at the interface between the mold and the prepolymer solution. When the drooping hydrophilic polymer chains are present in the prepolymer in a sufficient amount, an interfacial film, which is essentially composed of drooping hydrophilic polymer chains and has adequate thickness, can be formed at the mold-solution interface before curing (polymerization) and subsequently preserved after curing. As such, it is possible to manufacture a silicone hydrogel contact lens with a hydrophilic interfacial film on it, without any post-cure surface treatment.

There are several unique potential aspects associated with the use of the prepolymers of the invention in the manufacture of the silicone hydrogel contact lens. First, a prepolymer of the invention can be cured actinically16 on a time scale of seconds. Second, a lens forming formulation (polymerizable composition) can be a solution of the prepolymer that has been substantially purified (i.e., substantially removing the starting materials for making the prepolymer). It is not necessary to extract the lens after curing the lens. Third, the surface modification occurs before the lens is cured. No post-surface treatment is required. Fourth, the prepolymers of the invention can fully utilize the advantages provided by Lightstream Technology® in the manufacture of silicone hydrogel contact lenses at a relatively low cost and with high consistency and high fidelity to the original lens design.

The present invention, in one aspect, provides an actinically crosslinkable prepolymer. The prepolymer of the invention comprises: in the copolymer chain of the prepolymer, (1) siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers; (2) hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; and (3) pendant hydrophilic polymer chains that are covalently attached to the copolymeric chain and derived from at least one preformed hydrophilic polymer having a single crosslinkable group, wherein the pendant hydrophilic chains are free from actinically crosslinkable groups, wherein the hydrophilic polymer preform has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer, but high enough to provide a silicone hydrogel contact lens, which is obtained from the prepolymer, with an angle of contact with water of about 90 degrees or less, without surface post-curing treatment and when it is present in the prepolymer in an amount of about 2% to about 30% by weight, wherein the prepolymer is capable of being actinically crosslinked, in the absence of one or more monomers, to form the silicone hydrogel contact lenses.

A prepolymer of the invention comprises several actinically crosslinkable groups selected from the group consisting of ethylenically unsaturated groups and thiol groups.

When the crosslinking of a prepolymer of the invention is based on the mechanism of free radical chain growth polymerization, the prepolymer preferably comprises at least three ethylenically unsaturated groups.

When the crosslinking of a prepolymer of the invention is based on the polymerization mechanism of the thiolene stage growth radical, the actinically crosslinkable groups of the prepolymer preferably comprise at least three thiol groups or at least three groups containing ene. A group containing eno is intended to describe a monovalent or divalent radical that contains a double carbon-carbon that is not directly linked to a carbonyl group (-CO-), nitrogen atom or oxygen atom, being preferably defined by any of the formulas

<img file="BRPI0809151A2_D0001.tif" />

where R-ι is hydrogen or C1-C10 alkyl; R2 and R3 are independently hydrogen, divalent C1-C10 alkene radical, C1-C10 alkyl or (Rie) a- (Xi) b-Ri9 where R₁₈ is divalent C1-C10 alkene radical, Χ_Ί is an ether bond (-O-), an urethane bond (-N), a urea bond, an ester bond, an amide or carbonyl bond, R₁₉ is hydrogen, a single bond, amino group, carboxylic group, hydroxyl group, carbonyl group, C1-C-12 aminoalkyl group, QC-is alkylaminoalkyl group, C1-C18 carboxyalkyl group, CiC-ie hydroxyalkyl group, Ci-C group₁₈ alkylalkoxy, C-1-C12 aminoalkoxy group, C1-C12 alkylaminooxy group, Ci-Ci group₈ carboxyalkoxy or Cr Ci group₈ hydroxyalkoxy, a and b are independently zero or 1, as long as only one of R₂ and R₃ be a divalent radical; R₄ - Rg, ​​are independently hydrogen, radical Ci-C₁₀ divalent alkene, C1-C10 alkyl or - (Ris) to (Xi) b-Ri9&gt; optionally R₄ and Rg are linked via a divalent alkene radical to form a cyclic ring, as long as at least one of R₄ Rg is radical divalent; nor are they independently whole numbers from 0 to 9, as long as the sum of nor is an integer from 2 to 9; R₁₀ R17, are independently hydrogen, divalent C1-C10 alkene radical, C1C10 alkyl or - (Ri₈)_The- (Xi) b-Ri9. p is an integer from 1 to 3, as long as only one or two of R₁₀ - R17 are divalent radicals.

When the prepolymer comprises multiple groups containing ene, these groups undergo polymerization of growth radical in thiol-ene stages in the presence of thiol groups that can be provided by a step-growth crosslinking agent having two or more thiol groups. Similarly, when the prepolymer comprises multiple thiol groups, these groups undergo thiol-ene growth radical polymerization in the presence of ene-containing groups that can be provided by a step-growth cross-linking agent having two or more groups containing eno.

According to the invention, the hydrophilic polymer chains dangling from the prepolymer are each free from any actinically crosslinkable groups. The pendant hydrophilic polymeric chains are present in the prepolymer in an amount sufficient to provide a silicone hydrogel material, obtained by curing the prepolymer, a hydrophilic surface without surface post-curing treatment.

The hydrophilic polymer chains dangling from the prepolymer are derived from at least one preformed hydrophilic polymer having a single crosslinkable group. The only crosslinkable group can be any functional group capable of participating in a covalent coupling reaction described below or any actinically crosslinkable group which can participate in a polymerization to prepare an intermediate copolymer described below. The hydrophilic polymer preformed with a single crosslinkable group has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer. It is believed that if the molecular weight of the preformed hydrophilic polymer is too high, the covalent incorporation of the preformed hydrophilic polymer into the prepolymer would not be efficient in a coupling, especially in a free radical polymerization. Pre-formed non-crosslinked hydrophilic polymer is removed during ultrafiltration of the prepolymer. In addition, the hydrophilic polymer preformed with a single crosslinkable group has a molecular weight high enough to provide a silicone hydrogel contact lens, which is obtained from the prepolymer with an angle of contact with water of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, without post-cure surface treatment and when present in the prepolymer in an amount of about 2% to about 30% by weight. According to the invention, the molecular weight of a preformed hydrophilic polymer is from about 500 Daltons to about 20,000 Daltons, preferably about 1,000 Daltons to about 10,000 Daltons, more preferably about 2,000 Daltons to about 6,000 Daltons .

A prepolymer of the invention comprises: about 15% to about 70% by weight, preferably about 25% to about 80% of siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers; about 10% to about 80%, preferably about 15% to 45% by weight, of hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; and about 2% to about 30%, preferably about 4% to about 20% by weight of pendant hydrophilic polymer chains derived from one or more preformed and crosslinkable hydrophilic polymers.

According to the invention, a prepolymer of the invention can be obtained from an intermediate copolymer with pendant or terminal functional groups and pendant hydrophilic polymer chains by actinically crosslinkable groups of covalent attachment to the intermediate copolymer through the pendant or terminal functional groups, according to any covalent coupling method.

It is well known in the art that a pair of paired reaction groups can form a covalent bond under known coupling reaction conditions, such as oxidation-reduction conditions, condensation conditions by dehydration, addition conditions, substitution conditions (or displacement), Dieis-Alder reaction conditions, cationic crosslinking conditions and epoxy stiffening conditions. For example, an amino group reacts with an aldehyde group to form a Schiff base that can be further reduced; an amino group reacts with an acid chloride to form an amide bond (-CO-N); an amino group reacts with an isocyanate to form a urea bond; a hydroxyl reacts with an isocyanate to form an urethane bond; a hydroxyl reacts with an epoxy to form an ether (-O-) bond; a hydroxyl reacts with an acid chloride to form an ester bond.

Exemplary covalent bonds that are formed between pairs of crosslinkable groups include, without limitation, ester, ether, acetal, ketal, vinyl ether, carbamate, urea, urethane, amine, amide, enamine, imine, oxime, amidine, imino ester, carbonate, orthoester, phosphonate, phosphinate, sulfonate, sulfinate, sulfide, sulfate, disulfide, sulfinamide, sulfonamide, thioester, aryl, silane, siloxane, heterocycles, thiocarbonate, thiocarbamate and phosphonamide.

Exemplary reactive groups include hydroxyl group, amine group, amide group, anhydride group, sulfhydryl group, -COOR (R and R 'are hydrogen or C1-C alkyl groups₈), halide (chloride, bromide, iodide), acyl chloride, isothiocyanate, isocyanate, monochlorothriazine, dichlorotriazine, mono or dialogene substituted pyridine, mono or dialogene substituted diazine, phosphoramidite, maleimide, aziridine, sulfonuclear halide, hydroxy hydroxysulfosuccinimide ester, imido ester, hydrazine, axidonitrophenyl group, azide, 3- (2-pyridyl dithio) propionamide, glyoxal, aldehyde, epoxy.

It is understood that coupling agents can be used.

For example, a carbodiimide can be used in the coupling of a carboxyl and an amine to form an amide bond between the molecules being coupled. Examples of carbodiimides are 1-ethyl-3- (3dimethylaminopropyl) carbodiimide (EDC), N, N'-dicyclohexylcarbodiimide (DCC), 1-cyclohexyl-3- (2-morpholinoethyl) carbodiimide , diisopropyl carbodiimide or mixtures thereof. N-hydroxysuccinimide (NHS) or Nhydroxysulfosuccinimide can be desirably included in the carbodiimide-mediated coupling reaction (for example, EDC) to improve the efficiency of the coupling (conjugation). EDC couples NHS to carboxyls, resulting in an NHS-activated site in a molecule. The NHS ester formed can react with amines to form the amides.

Preferably, the intermediate copolymer functional group is selected from the group consisting of hydroxyl groups (-OH), primary amino groups (-NH2), secondary amino groups (-NHR), carboxyl groups (COOH), epoxy groups, aldehyde groups (- CHO), amide groups (-CONH₂), acid halide groups (-COX, X = Cl, Br or I), isothiocyanate groups, isocyanate groups, halide groups (-X, X = Cl, Br or I), acid anhydride groups and combinations thereof.

Any copolymers that include siloxane units derived from a siloxane-containing monomer or macromer, hydrophilic units derived from a hydrophilic monomer or polymer in the copolymer chain, pendant hydrophilic polymer chains and pendant or terminal functional groups can be used as an intermediate copolymer in the invention. Such a copolymer would be soluble in water, an organic solvent, a mixture of water and at least one organic solvent or a mixture of organic solvents.

An intermediate copolymer can be obtained by copolymerizing a mixture comprising (a) at least one compound containing linear siloxane with two first and second terminal functional groups (i.e., having two functional groups, one at each of the two opposite ends) (b) at least one linear hydrophilic monomer or polymer with two first and second terminal functional groups, (c) at least one hydrophilic polymer with only one first or second functional group and (d) one or more branching agents which independently of one another are an organic compound with three or more first or second functional groups, wherein the first and second functional groups second functional groups are different from each other and selected from the group consisting of the amine, hydroxyl, carboxy, isocyanate, epoxy and acid halide group, in which the first and second functional groups are different from gold, but correative to each other in the presence or absence of a coupling agent to form a covalent bond selected from the group consisting of urethane, urea, ether and amide, where the ratio of molar equivalents of the first functional groups to the second functional groups or second functional groups for the first functional groups in the mixture is about 1.1 to about 20, preferably from 1.1 to about 5, more preferably from about 1.1 to about 3.

When the first functional groups are amine groups and the second functional groups are isocyanate group, the intermediate copolymers obtained are polyureas capped with amine.

When the first functional groups are isocyanate groups and the second functional groups are amine groups, the intermediate copolymers obtained are polyureas capped with isocyanate.

When the first functional groups are hydroxy groups and the second functional groups are isocyanate group, the intermediate copolymers obtained are polyurethanes capped with hydroxy.

When the first functional groups are isocyanates and the second functional groups are hydroxy groups, the intermediate copolymers obtained are polyurethanes capped with isocyanate.

When the first functional groups are amine groups and the second functional groups are acid halide groups, the intermediate copolymers obtained are polyamides capped with amine.

When the first functional groups are amine groups and the second functional groups are carboxyl groups, the intermediate copolymers obtained in the presence of EDC are amine-capped polyamides.

When the first functional groups are carboxyl groups and the second functional groups are amine groups, the intermediate copolymers obtained in the presence of EDC are polyamides capped with carboxyl.

When the first functional groups are hydroxy groups and the second functional groups are epoxy groups the intermediate copolymers obtained are polyether capped with hydroxy.

Exemplary linear siloxane compounds with two selected terminal functional groups, consisting of amino groups, hydroxyl groups, acid chloride groups and epoxy groups are polysiloxane terminated in a difunctional group, such as, for example, poly (dialkylsiloxane), poly (diarylsiloxane), polyarylalkylsiloxane , copolymers of different dialkylsiloxanes, copolymers of dialkylsiloxane with diarylsiloxane or arylalkylsiloxane, or the like. Preferably, a compound containing siloxane is a difunctional group-terminated polydimethylsiloxane. Various functional polysiloxanes terminated in a difunctional group can be obtained from commercial suppliers (for example, from Gelest, Inc., or Fluorochem). Otherwise, one skilled in the art will know how to prepare such polysiloxanes terminated in a difunctional group according to procedures known in the art and described in the Journal of Polymer Science - Chemistry, 33, 1773 (1995) (incorporated herein in its entirety as reference).

Exemplary hydrophilic monomers or macromers with two selected terminal functional groups and consisting of amino groups, hydroxyl groups, acid chloride groups and epoxy groups are poly (ethylene glycol) (PEG) terminated in a difunctional group, block copolymers terminated in a difunctional oxide group. ethylene and propylene oxide ((PEG / PPG block copolymers, for example, poloxamers or poloxamine), polyalkylacrylamides of polymers terminated from difunctional group, difunctional group-terminated polyalkylmethacrylamides, difunctional group-terminated polyvinylpyrrolidones, difunctional group-terminated copolymers of Nvinylpyrrolidone with one or more vinyl monomers (such as, for example, dialkylaminoalkyl acrylate, dialkylamino, dialkylamine; , vinyl acetate or mixtures thereof), polyvinyl alcohols terminated in diamine or dicarboxyl (derived from methanolysis or hydrolysis of polyvinyl acetates terminated in a functional group) and copolymers terminated in a difunctional group (preferably subjected to methanolysis or hydrolysis) of vinyl acetate with one or more vinyl monomers (for example, acrylate acrylate) dialkylaminoalkyl, dialkylaminoalkyl methacrylate, N, N-dialkylacrylamide, Ν, Νdialkylmethacrylamide or mixtures thereof).

Various amine-terminated PEGs, hydroxyl-terminated PEGs and epoxy-terminated PEGs can be obtained from commercial suppliers, such as Polyscience and Shearwater Polymers, Inc., etc.

According to the invention, any hydrophilic vinyl monomers without primary amino group, hydroxyl group, isocyanate group or epoxy group can be used in the preparation of precursor polymers or copolymers terminated in a difunctional group. Examples of such hydrophilic vinyl monomers include N, N-dialkylacrylamide, Ν, Ν-dialkylmethacrylamide, N-vinylpyrrolidone (NVP), dialkylaminoalkyl acrylate, dialkylaminoalkyl methacrylate. Examples of preferred hydrophilic polymers or copolymers terminated in difunctional group include poly (N, N-dimethylacrylamide (poly (DMA)) terminated in difunctional group, poly (N-vinylpyrrolidone) (PVP) terminated in difunctional group, terminated DMA / NVP copolymers in difunctional groups, copolymers terminated in NVP methacrylate / dimethylaminoethyl difunctional group, DMA / N-octylacrylamide copolymer terminated in difunctional group, NVP / N-octylacrylamide copolymers terminated in a difunctional group, diamine-terminated polyvinyl alcohol, dicarboxyl-terminated polyvinyl alcohol, diamine-terminated vinyl acetate / NVP copolymer (preferably subjected to methanolysis or hydrolysis), vinyl acetate / NVP copolymer dicarboxyl (preferably subjected to methanolysis or hydrolysis), diamine-terminated vinyl acetate / DMA copolymer (preferably subjected to methanolysis or hydrolysis), dicarboxyl-terminated vinyl acetate / DMA copolymer (preferably subjected to methanolysis or hydrolysis) and the like.

Precursor polymers or copolymers terminated in dihydroxy or diamine may be prepared according to the procedures described in US Patent No. 6,218,508, incorporated herein in their entirety by reference. For example, one or more hydrophilic vinyl monomers without primary amino group, hydroxyl group, isocyanate group, carboxyl or epoxy group and a chain transfer agent (for example, 2-mercaptoethanol, 2-aminoethanethiol, 2-mercaptopropynic acid, thioglycolic acid , thiolactic acid or other hydroxy mercaptans, aminomercaptans or mercaptans containing carboxyl) are copolymerized (thermally or actinically) with a vinyl monomer with a hydroxyl, carboxyl or amine group, in the presence of an initiator. Preferably, the polymerizable mixture for preparing such precursor polymers or copolymers is substantially free of crosslinking agent (i.e., a compound having two or more ethylenically unsaturated groups).

The chain transfer agent with amine, hydroxyl or carboxyl group can be used to control the molecular weight of the resulting polymer or copolymer and provide functionality (amine, hydroxyl or carboxyl group) for subsequent functionalization of the resulting polymer or copolymer. The chain transfer agent forms a terminal end of the resulting hydrophilic polymer or copolymer with the hydroxyl, amine or carboxyl group providing the resulting polymer or copolymer with a hydroxyl, amine or carboxy terminal group. The vinyl monomer containing hydroxyl, carboxyl or amine provides another amino, carboxyl or hydroxyl functionality to the resulting polymer or copolymer.

In general, the molar ratio of the chain transfer agent to that of one or more hydrophilic vinyl monomers is from about 1: 5 to about 1: 100, considering that the molar ratio of the chain transfer agent to the vinyl monomer with a hydroxyl or amino group is 1: 1. The molar ratio of the chain transfer agent to the hydrophilic vinyl monomer without primary amino group, hydroxyl group, isocyanate group or epoxy group (for example, DMA, NVP) is selected to obtain a polymer or copolymer with a molecular weight preferably of about 200 to about 4,000, more preferably about 500 to about 2,500 Daltons. It is understood that the resulting polymer or copolymer can be polymerized in the presence of a diisocyanate to obtain a new polymer or copolymer with a higher molecular weight and two terminal hydroxyl or amine groups. Any alkyl or aryl diisocyanates can be used for this purpose. Preferred diisocyanates include isophorone diisocyanate, hexamethyl 1,6-diisocyanate, 4,4'-dicyclohexylmethane diisocyanate, toluene diisocyanate, 4,4'-diphenyl diisocyanate, diisocyanate of 4,4'-diphenylmethane, p-phenylene diisocyanate, diisocyanate of

1,4-phenylene 4,4'-diphenyl,

1,3-bis- (4,4'-methyl isocyanate) cyclohexane and cyclohexane diisocyanate.

Precursor polymers or copolymers terminated in diepoxy, diisocyanate or diacid chloride of one or more hydrophilic vinyl monomers can be prepared by covalently attaching epoxy, isocyanate or acid chloride groups with respect to the diamine or dihydroxy polymers or copolymers obtained above of one or more hydrophilic vinyl monomers according to any known procedures.

Exemplary hydrophilic precursor polymers or copolymers with a terminated functional group selected from the group consisting of amino group, hydroxyl group, acid chloride group, carboxyl group and epoxy group, are hydrophilic polymers terminated in a monofunctional group including poly (ethylene glycol) (PEG) terminated in monofunctional group, PEG / PPG block copolymers terminated in monofunctional group, polyalkylacrylamides terminated in monofunctional group, monofunctional group-terminated polyalkylmethacrylamides, monofunctional group-terminated polyvinylpyrrolidines, Nvinylpyrrolidone monofunctional group-terminated copolymers with one or more vinyl monomers (such as, for example, dialkylaminoalkyl acrylate, dialkyl methacrylate, dialkyl acrylate, dialkyl acrylate) ; vinyl acetate or mixtures thereof), polyvinyl alcohols terminated in a monofunctional group (derived from methanolysis or hydrolysis of polyvinyl acetates terminated in a functional group) and copolymers terminated in a monofunctional group (preferably subjected to methanolysis or hydrolysis) of vinyl acetate with one or more vinyl monomers (for example, vinyl acrylate) dialkylaminoalkyl, dialkylamino methacrylate, Ν, Ν-dialkylacrylamide, N, N-dialkylmethacrylamide or mixtures thereof).

Various monofunctional terminated PEGs can be obtained from Shearwater Polymers, Inc. Preferred monofunctional terminated PEGs are those PEGS with an amino, hydroxyl, acid chloride or epoxy group at one end group and a methoxy or ethoxy at the other end.

Precursor polymers or copolymers terminated in a monofunctional group can be prepared according to procedures similar to those described in US Patent No. 6,218,508 incorporated herein by reference in their entirety. For example, one or more hydrophilic vinyl monomers without functional group (i.e., primary amino group, hydroxyl group, isocyanate group, carboxyl group or epoxy group) and a chain transfer agent (for example, 2-mercaptoethanol, 2aminoethanethiol, acid 2-mercaptopropinic, thioglycolic acid, thiolactic acid or other hydroxy mercaptans, aminomercaptanes or mercaptans containing carboxyl) are copolymerized (thermally or actinically) in the presence or absence of an initiator to obtain a monohydroxy, monocarboxyl or monoamine-terminated hydrophilic polymer or copolymer. In general, the molar ratio of the chain transfer agent to that of one or more hydrophilic vinyl monomers is from about 1: 5 to about 1: 100. The molar ratio of the chain transfer agent to the hydrophilic vinyl monomer without functional group (for example, DMA, NVP) is selected to obtain a polymer or copolymer with a molecular weight of about 500 to about 20,000, preferably about 1,000 to about 10,000, more preferably about 2,000 to about 6,000 Daltons. Polymers or copolymers terminated in monoeppoxy, monoisocyanate or mono acid chloride of one or more hydrophilic vinyl monomers can be prepared by covalently attaching epoxy, isocyanate or acid chloride groups to polymers or copolymers terminated in monohydroxy or monoamine obtained above 28 more hydrophilic vinyl monomers according to known procedures. The use of polymers or copolymers terminated in a higher molecular weight monofunctional group can ensure that the interfacial film over a silicone hydrogel material or lens manufactured from a prepolymer of the invention has adequate thickness and coverage.

Alternatively, precursor polymers or copolymers terminated in a monofunctional group can be prepared by polymerizing one or more hydrophilic monomers in the presence of a free radical initiator containing hydroxyl, amine or carboxyl in a molar ratio of initiator to hydrophilic monomers of about 1: 30 to about 1: 700. Examples of initiators with amine, hydroxyl or carboxy groups are azo initiators, such as, for example, 2,2'-Azobis {2- [1- (2-hydroxyethyl) -2imidazolin-2-yl] propane dihydrochloride, 2 , 2'-Azobis {2-methyl-N- [1,1-bis (hydroxymethyl) -2hydroxyethyljpropionamide, 2,2'-Azobis [2-methyl-N- (2-hydroxyethyl) propionamide] or 2,2'- Azobis {2-methyl-N- [2- (1-hydroxybutyl)] propionamide}, 2,2'Azobis (2-methylpropionamide) dihydrochloride, 2,2'-azobis [N- (2-carboxyethyl) -2methylpropionamidine tetrahydrate] or the like.

Other examples of preferred monoethylenically functionalized hydrophilic polymers include, without limitation: polyoxazoline terminated in mono (meth) acrylate; poly (methacrylate-co-mono (meth) acrylate PEG) terminated in mono (meth) acrylate); poly (glycerol methacrylate) terminated in mono (met) acrylate; poly (diethylaminoethyl (meth) acrylate) terminated in mono (meth) acrylate); poly (dimethyl acrylamide) terminated in mono (meth) acrylate; poly (dimethyl acrylamide) terminated in mono (meth) acrylamide); and monoethylenically functionalized hydrophilic polymer with short, pendant PEG chains (i.e., PEG having a molecular weight of less than about 400 Daltons).

Where hydrophilic precursor polymers or copolymers terminated in a mono or difunctional group are polyvinyl alcohols or polyvinyl alcohol copolymers the terminal functional groups are preferably amine or carboxyl groups. In general, isocyanate groups would first react with amine groups even in the presence of hydroxyl groups. In addition, the amine groups or carboxy groups will participate in the EDC-mediated coupling reaction, considering that the hydroxyl groups do not.

Examples of preferred triamine or polyamines include, without limitation, diethylenetriamine, N-2'-aminoethyl-1,3-propylenediamine, N, N-bis (3aminopropyl) -amine, N, N-bis (6-aminohexyl) amine and triethylenetetramine.

Examples of preferred triisocyanates include, without limitation, the hexamethylene diisocyanate isocyanurate trimer, sodium triisocyanurate

2,4,6-toluene, p, p 'triisocyanate, p-triphenylmethane, and the isophorone diisocyanate trifunctional trimer (isocyanurate). Preferably, a polyisocyanate is a C6-C45 cycloaliphatic or aliphatic-cycloaliphatic compound containing 4-6 isocyanate groups and at least one heteroatom selected from the group consisting of oxygen and nitrogen.

Examples of organic triols or polyols are glycerol, diglycerol, triglycerol, 1,1,1-trishydroxymethylethane, 1,1,1-trishydroxymethylpropane, 1,2,4-butanotriol, 1,2,6-hexanotriol, erythritol, pentaerythritol, di- or tripentaerythritol, arabitol, sorbitol, disorbitol or mannitol and mixtures thereof.

Preferred tri or polyacid halides (i.e., di or polycarbonyl chloride) are tracid chlorides, tracid brometers, diacid chlorides and diacid bromides. Examples of tracid chlorides are trimesoyl chloride, cyclohexane-1,3,5-tricarbonyl chloride, trimer acid chloride and the like.

Examples of tri and polypoxy compounds are compounds from the DENACOL series supplied by Nagase and triglycidylisocyanurate (TGIC).

In a preferred embodiment, a branching agent is an organic compound comprising three functional groups, wherein the functional groups are selected from the group consisting of amino groups, hydroxyl groups, acid chloride groups and epoxy groups.

According to the invention, a prepolymer of the invention can also be obtained from an intermediate copolymer with terminal or pendant functional groups, but without pendant hydrophilic polymer chains by covalently attaching actinically crosslinkable groups and at least one hydrophilic polymer terminated in a monofunctional group to the copolymer. in30 termediary via terminal or pendant functional groups, according to any covalent coupling method.

According to the invention, a prepolymer of the invention can additionally be obtained from a prepolymer having multiple actinically crosslinkable groups and functional terminal and pendant groups, but without pendent hydrophilic polymer chains, by covalently attaching at least one hydrophilic polymer terminated in a monofunctional group to the intermediate copolymer through terminal or pendant functional groups, according to any covalent coupling method.

The mixture for preparing an intermediate copolymer can be a melt (without solvent) or a solution where all the necessary components are dissolved in an inert solvent (that is, it does not interfere with the reaction between the reactants in the mixture), such as water, an organic solvent or mixture thereof, as known by the skilled person.

Examples of organic solvents include, but are not limited to, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, diethylene glycol ether, diethylene glycol methyl ether, ethylene glycol methyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycol ether, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, lactate methyl, ethyl lactate, i-propyl lactate, methylene chloride, 2-butanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2hexanol, 3-hexanol, 3- methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2decanol, 3-octanol, norborneol, f-butanol, tert-amyl, alcohol, 2-methyl-2 pentanol, 2,3-dimethyl-2-butanol, 3-methyl- 3-pentanol, 1-methylcyclohexanol, 2methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2heptanol, 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-431 octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene, 4-hydroxy-4methyl-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-2propanol and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2 -propanol, tamil alcohol, isopropanol, 1-methyl-2-pyrrolidone, Ν, Ν-dimethylpropionamide, dimethyl formamide, dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone and mixtures thereof.

The reaction temperature may vary depending on the type of reaction. For example, for an amine isocyanate or amine acid chloride reaction, the temperature can be in the range of -20 to 85 ° C, preferably of -10 to 50 ° C and more preferably of -5 to 30 ° C. Reaction times may vary within wide limits, a time of approximately 1 to 10 hours, preferably 2 to 8 hours and more preferably 2 to 3 hours having been proven to be practicable.

Reaction times can vary within wide limits. The reaction can be monitored by controlling the consumption of one or more functional groups that participate in the reaction.

It is understood that some reactions are preferably carried out in the presence of a catalyst. For example, the hydroxyisocyanate reaction is advantageously carried out in the presence of a catalyst, since the reaction time can be significantly shortened. Suitable catalysts are, for example, metal salts, such as alkali metal salts or tin salts of organic carboxylic acids or tertiary amines, for example, (C 1 -C 6 -alkyl) 3N (triethylamine, tri-n-butylamine) , Nmethylpyrrolidine, N-methylmorpholine, Ν, Ν-dimethylpiperidine, pyridine or 1,4-diazabicyclooctane. Tin salts have proved to be particularly effective, especially alkyl-tin salts of carboxylic acids, for example, dibutyl tin dilaurate (DBTDL) and tin dioctoate.

Alternatively, intermediate copolymers with pendant or terminal functional groups can be prepared by actinic or thermal polymerization, a polymerizable mixture of components comprising components with one or more actinically unsaturated groups or thiol groups.

In a preferred embodiment, the intermediate copolymer with pendant or terminal functional groups is obtained by copolymerizing an actinically polymerizable composition comprising (1) at least one monoethylene functionally hydrophilic polymer (i.e., with a single ethylenically unsaturated group), (2) by least one hydrophilic vinyl monomer (that is, having an ethylenically unsaturated group), (3) at least one siloxane-containing monomer having an ethylenically unsaturated group, at least one silane-containing macromer having an ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one silane-containing macromer having two or more ethylenically unsaturated groups or a combination of two or more of them, (4) optionally at least one di or multiethylenically functionalized hydrophilic polymer and / or at least one hydrophilic crosslinker (i.e., having two or more ethylenically unsaturated groups) with a molecular weight of less than 700 Daltons; and (5) optionally at least one hydrophobic vinyl monomer, provided that at least one of the components (2) - (4) additionally comprises at least one functional group through which an ethylenically crosslinkable group (ethylenically unsaturated group or thiol group) can be covalently bound to the obtained copolymer.

In another preferred embodiment, the intermediate copolymer with pendant or terminal functional groups is obtained by copolymerizing a composition comprising (1) at least one monoethylene functionally hydrophilic polymer (i.e., with a single ethylenically unsaturated group), (2) at least one hydrophilic vinyl monomer (i.e., having an ethylenically unsaturated group), (3) at least one siloxane-containing monomer having an ethylenically unsaturated group, at least one silane-containing macromer having an ethylenically unsaturated group, at least one siloxane-containing monomer having two or more ethylenically unsaturated groups, at least one silane-containing macromer having two or more ethylenically unsaturated groups or a combination of two or more of them, ( 4) optionally at least one di or multiethylenically functionalized hydrophilic polymer and / or at least one hydrophilic crosslinker (i.e. presenting two or more ethylenically unsaturated groups) with a molecular weight of less than 700 Daltons; (5) optionally at least one hydrophobic vinyl monomer, and (6) at least one chain transfer agent having a functional group through which an ethylenically cross-linkable group (ethylenically unsaturated group or thiol group) can be covalently bonded to the obtained copolymer.

According to the invention, mono, di or multiethylenically functionalized hydrophilic polymers can be prepared by covalently attaching one or more ethylenically unsaturated groups to the functional groups (for example, amine, hydroxyl, carboxyl, isocyanate, epoxy groups) of a polymer or mono, di or multifunctionalized hydrophilic copolymers (i.e., with one or more functional groups). Any vinyl monomer having a hydroxy, amino, carboxyl, epoxy, acid chloride, isocyanate group, which is correative with isocyanate, amine, hydroxyl, carboxy or epoxy groups of a polymer or copolymer in the absence or presence of a coupling agent (such as , for example, EDC, diisocyanate or diacid chloride) can be used in ethylene functionalization of the precursor polymer or copolymer. Examples of such vinyl monomers include, without limitation, for reaction with terminal hydroxy groups, 2-isocyanatoethyl methacrylate, methacrylic anhydride, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, acryloyl chloride or methacrylyl chloride, glycidyl methacrylate; for reaction with terminal amine groups, 2-isocyanatoethyl methacrylate, 3isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, methacrylic anhydride, acrylic acid, methacrylic acid, acrylyl chloride or methacrylyl chloride; for reaction with terminal carboxy groups in the presence of EDC, vinylamine, 2-aminoethyl methacrylate or 3-aminopropyl methacrylamide. The above list is not exhaustive but illustrative. One skilled in the art will know how to select a vinyl monomer with a functional group to ethylene-functionalize polymers or hydrophilic precursor copolymers.

Examples of hydrophilic mono, di or multiethylenically functionalized polymers include, without limitation, hydrophilic polymers or copolymers

Ios having an acryloyl (CH) terminal₂-c — CO—), methacryloyl

CH₃ _ I (CH₂-c — co—) or vinyl group; hydrophilic polymers or copolymers with two terminal acryloyl, methacryloyl or vinyl groups; and hydrophilic polymers or copolymers with multiple acryloyl, methacryloyl or vinyl groups (i.e., 3 or more). The hydrophilic polymers or copolymers are preferably selected from the group consisting of: PEGs; PEG / PPG block copolymers; polyalkylacrylamides; polyalkylmethacrylamides; polyvinylpyrrolidones; copolymers of N-vinylpyrrolidone with dialkylaminoalkyl acrylate (for example, dimethylaminoethyl acrylate), dialkylaminoalkyl methacrylate (for example, dimethylaminoethyl methacrylate), vin, Ν-dialkylacrylamide, N, acetyl; polyvinyl alcohols (derived from polyvinyl acetates); copolymers of vinyl acetate with dialkylaminoalkyl acrylate (for example, dimethylaminoethyl acrylate), dialkylaminoalkyl methacrylate (for example, dimethylaminoethyl methacrylate), N, dialkylacrylate, Ν, or qu-dialkyl acetate.

Monoethylenically functionalized PEGs or PEG / PPG block copolymers and diethylenically functionalized PEGs or PEG / PPG block copolymers are either commercially available or can be prepared by covalently attaching acryloyl, methacrylyl or vinyl groups to block copolymers or PEGS groups terminated in monofunctional groups. ethylene oxide and propylene oxide and block copolymers or PEGs terminated in a difunctional group of ethylene oxide and propylene oxide.

A monoethylenically functionalized polymer or copolymer means that the polymer or copolymer has a simple ethylenically unsaturated group. A diethylenically functionalized polymer or copolymer means that the polymer or copolymer has only two ethylenically unsaturated groups.

Mono or diethylenically functionalized polyalkylacrylamides, polyalkylmethacrylamides, polyvinylpyrrolidones; Copolymers of Nvinylpyrrolidone with one or more vinyl monomers, polyvinyl alcohols (derived from polyvinyl acetates) or vinyl acetate copolymers with one or more vinyl monomers can be prepared from their polymers or precursor copolymers terminated in the corresponding mono functional group described above.

Where the hydrophilic precursor polymers or copolymers terminated in the mono or difunctional group are polyvinyl alcohols or polyvinyl alcohol copolymers, the terminal functional groups are preferably amine or carboxyl groups. In general, isocyanate groups would react first with amine groups, even in the presence of hydroxyl groups. Also, the amine groups or carboxy groups will participate in the coupling reaction mediated by EDC, considering that the hydroxyl groups do not.

According to the invention, multiethylenically functionalized hydrophilic polymers are derived from hydrophilic precursor polymers or copolymers containing multiple terminal and / or pendant functional groups (for example, -NH₂, -COOH, -OH). Examples of such hydrophilic precursor copolymers are the copolymers of N-vinylpyrrolidone, N, Ndialkylacrylamide, Ν, Ν-dialkylmethacrylamide, dialkylaminoalkyl methacrylate or dialkylaminoalkyl acrylate with at least one vinyl monomer group consisting of vinyl acetate group acrylic, methacrylic acid, hydroxylalkyl acrylate, hydroxymethacrylate, amino acrylate, and aminoalkyl methacrylate. The percentage of units derived from vinyl monomer containing functional group is preferably less than about 15%, more preferably less than about 10%, even more preferably less than about 5% by weight.

According to the invention, the monoethylenically functionalized hydrophilic polymer has a molecular weight of about 500 to about 20,000, preferably about 1,000 to about 10,000, more preferably about 2,000 to about 6,000 Daltons.

It is to be understood that a mixture of one or more monoethylenically functionalized hydrophilic polymers and one or more diethylenically functionalized hydrophilic polymers can be used advantageously in the preparation of the intermediate copolymer, the precursor of a prepolymer of the invention.

Almost all hydrophilic vinyl monomers can be used in the actinically polymerizable composition for preparing the intermediate copolymer with pendant or terminal functional groups. Suitable hydrophilic vinyl monomers are, without being an exhaustive list, Ci-C₈ alkylacrylates and methacrylates substituted with hydroxyl, acrylamide, methacrylamide, Ci-Cs alkylacrylamides, C-pCg alkylmethacrylamides, ethoxylated acrylates, ethoxylated methacrylates, Ci-C₈ hydroxyl-substituted alkylacrylamides, hydroxyl-substituted alkylmethacrylamides, hydroxyl-substituted lower alkyl vinyl ethers, sodium vinylsulfonate, sodium styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic acid, Nvinylpyrrolidone-2-pyridoline, N-vinyl pyrrolidone, N-vinyl pyrrolidone , 2-vinyl 4,4'-dialkyloxazolin-5one, 2- and 4-vinylpyridine, vinyl unsaturated carboxylic acids having a total of 3 to 5 carbon atoms, amino (lower alkyl) - (where the term amino also includes quaternary ammonium), mono (lower alkylamino) (lower alkyl) and di (lower alkylamino) (lower) alkyl acrylates and methacrylates), allyl alcohol, N-vinyl alkylamide, N-vinyl-N-alkylamide, and the like.

Preferred hydrophilic vinyl monomers include N, Ndimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), methacryloxymethyl hydrochloride 2 , aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, N (1,1dimethyl-3-oxobutyl) acrylamide, acrylic acid, C1-C4-alkoxy polyethylene glycol (meth) acrylate having a numerical average molecular weight of 200 to 1,500, methacrylic acid, N-vinyl formamide , N-vinyl acetamide, N-vinyl isopro37 pilamide, N-vinyl-N-methyl acetamide, allyl alcohol, and N-vinyl caprolactam.

Almost all hydrophilic vinyl monomers can be used in the actinically polymerizable composition for preparing the intermediate copolymer with pendant or terminal functional groups. Suitable hydrophobic vinyl monomers include, without limitation, Ci-Ciealkylacrylates and methacrylates, C₃-C-i8 alkylacrylamides and methacrylamides, acrylonitrile, methacrylonitrile, vinyl-Cq-C-is-alkanoates, C₂-Cis-alkenes, C₂-C-i8-haloalkenes, styrene, Ci-CQ-alkylstyrene, vinylalkyl ethers, where the alkyl portion has 1 to 6 carbon atoms, C₂-Ci₀-perfluoralkyl-acrylates and methacrylates or corresponding partially fluorinated acrylates and methacrylates, C3-Ci acrylates₂-perfluoralkyl-ethyl-thiocarbonylaminoethyl and methacrylates, acryloxy and methacryloxy-alkylsiloxanes, N-vinylcarbazole, C1-C12-alkyl esters of maleic acid, fumaric acid, itaconic acid, mesaconic acid and the like. Preference is given, for example, to C 1 -C 4 -alkyl esters of vinylically unsaturated carboxylic acids of 3 to 5 carbon atoms or vinyl esters of carboxylic acids with up to 5 carbon atoms.

Examples of preferred hydrophobic vinyl monomers include methacrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, ethyl acetate , vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyl toluene, ethyl vinyl ether, perfluoro-hexylethyl-thio-carbonyl-aminoethyl methacrylate, isobornyl methacrylate, trifluorethyl methacrylate, hexaflourisopropyl methacrylate, hexafluorbutyl methacryloxymethyl-propyl-methacryl-methylacrylate ld issiloxa no.

Any suitable siloxane-containing monomers or macromers known with one or more ethylenically unsaturated groups can be used in the ethylenically polymerizable composition for preparing the intermediate copolymer with pendant or terminal functional groups. Preferred examples of such monomers or macromers are monomethacrylated or monoacrylated polydime38 tylsiloxanes of various molecular weights (e.g., terminated with mono-3-methacryloxypropyl, polydimethylsiloxane terminated with monobutyl or terminated in mono- (3-methacryloxy-hydroxy-2-hydroxy) -hydro-propylated hydroxy monobutyl); diacrylated or dimethacrylated polydimethylsiloxanes of various molecular weights; vinyl-terminated polydimethylsiloxanes; vinyl-terminated polydimethylsiloxanes of various molecular weights; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; acrylate-terminated polydimethylsiloxanes; methacrylate-terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane; Ν, Ν, Ν ', Ν'tetracis (3-methacryloxy-2-hydroxypropyl) -alpha, omega-bis-3-aminopropylpolidimethylsiloxane; polysiloxanilalkyl (meth) acrylic monomers; macromer containing siloxane selected from the group consisting of Macromere A, Macromere B, Macromere C, and Macromere D described in US Patent No. 5,760,100 (incorporated herein in its entirety by reference); reaction products of glycidyl methacrylate with aminofunctional polydimethylsiloxanes; hydroxyl functionalized siloxane-containing monomers or macromers; macromers containing siloxane described in US Patent No. 6,762,264 (incorporated herein by reference in their entirety). Di- and triblock macromers consisting of polydimethylsiloxane and polyalkylene oxides would also be useful. For example, polyethylene oxide-block-polydimethylsiloxane-blocking polyethylene end capped with methacrylate can be used to improve oxygen permeability. Suitable monofunctional hydroxyl-functionalized siloxane monomers and appropriate multifunctional hydroxyl-functionalized siloxane monomers are commercially available from Gelest, Inc, Morrisville, PA.

The functional chain transfer agent is used to control the molecular weight of the resulting copolymer and to provide functionality for subsequent addition of a thiol group, a group containing ene, a portion of cinnamic acid, a dialkylmaleimide group. The chain transfer agent may comprise one or more thiol groups, for example, two or more, preferably one thiol group. Suitable chain transfer agents include primary organic thiols or mercaptans having an additional functional group, such as, for example, hydroxy, amino, carboxy or an appropriate derivative thereof. The chain transfer agent can be present in the polymerizable composition for making an intermediate copolymer in an amount of, for example, about 0.5 to about 5%, preferably about 1% to about 4%, and specifically about 1.5% to about 3.5% by weight, based on the combined weight of all polymerizable components.

Any suitable known vinyl monomer containing at least one functional group can be employed in the actinically polymerizable composition for preparing the intermediate copolymer with pendant or terminal functional groups. Preferred examples of such vinyl monomers include methacrylic acid (MAA), acrylic acid, glycidyl methacrylate, glycidyl acrylate, HEMA, HEA, methacrylic anhydride, N-hydroxymethylacrylamide (ΝΗΜΑ), 2-bromoethyl methacrylate, and vinylbenzyl chloride.

It should be understood that a vinyl monomer can be employed both as a hydrophilic vinyl monomer and as a functionalizing vinyl monomer in the actinically polymerizable composition for preparing the silicone-containing polymer with pendant or terminal functional groups. Preferably, the hydrophilic vinyl monomer is free of functional groups (for example, DMA, NVP).

The actinically polymerizable composition for preparing an intermediate copolymer can be a molten liquid, without solvent, in which all the necessary components are combined, preferably in the presence of one or more vinyl monomers in combination or a solution in which all the necessary component is dissolved in an inert solvent (that is, not interfering with the reaction between the reactants in the mixture), such as water, an organic solvent, or a mixture thereof, as known to one skilled in the art. Examples of solvents are as described above.

One or more vinyl monomers in combination are in an amount sufficient to dissolve both the hydrophilic and hydrophobic components of the actinically polymerizable composition. A vinyl monomer in combination refers to a vinyl monomer that can function as both a solvent to dissolve both the hydrophilic and hydrophobic components of an actinically polymerizable composition and as one of the polymerizable components to be polymerized to form a silicone hydrogel material. Preferably, the vinyl monomer in combination is present in the actinically polymerizable composition in an amount of about 5% to about 30% by weight.

Any suitable vinyl monomers capable of dissolving both hydrophilic and hydrophobic components of a polymerizable composition of the invention to form a solution can be used in the invention. Preferred examples of vinyl monomers in combination include, without limitation, aromatic vinyl monomers, vinyl monomers containing cycloalkyl. Those preferred vinyl monomers in combination can increase the predominant glass transition temperature of a hydrogel-silicone material prepared by curing a polymerizable composition containing that preferred combination monomer.

Examples of preferred aromatic vinyl monomers include styrene, 2,4,6-trimethylstyrene (TMS), f-butyl styrene (TBS), 2,3,4,5,6pentafluorostyrene, benzyl methacrylate, divinylbenzene and 2-vinylnaphthalene. Of these monomers, a monomer containing styrene is preferred. A styrene-containing monomer is defined herein as a monomer that contains a vinyl group attached directly to a phenyl group, where the phenyl group can be replaced by one other than a fused ring, for example, as above, with one to three C1-C6 alkyl groups. Styrene, properly [H₂C = CH-C₆H5] is a specifically preferred styrene-containing monomer.

A vinyl monomer containing cycloalkyl is defined herein as a vinyl monomer containing a cycloalkyl that can be substituted by up to three Ci-C groups₆ alkyl. Preferred vinyl monomers containing cycloalkyl include, without limitation, acrylates and methacrylates, each comprising a cyclopentyl or cyclohexyl or cycloheptyl, which can be substituted by up to three CiC groups₆ alkyl. Examples of preferred vinyl monomers containing cycloalkyl include isobornyl methacrylate, isobornyl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate and the like.

The copolymerization of a polymerizable composition for preparing an intermediate copolymer can be induced photochemically or preferably thermally. Suitable thermal polymerization initiators are known to those skilled in the art and comprise, for example, peroxides, hydroperoxides, azo-bis (alkyl- or cycloalkylnitriles), persulfates, percarbonates or mixtures thereof. Examples are benzoyl peroxide, tert-butyl peroxide, di-tert-butyl diperoxiftlate, tert-butyl hydroperoxide, azo-bis (isobutyronitrile) (AIBN), 1,1-azodi-isobutyramidine, 1,1'azo- bis (1-cyclohexanecarbonitrile), 2,2'-azo-bis (2,4-dimethylvaleronitrile) and the like. The polymerization is conveniently carried out in a solvent mentioned above at elevated temperature, for example at a temperature of 25 to 100 ° C and preferably 40 to 80 ° C. The reaction time can vary within wide limits, but it is conveniently, for example, 1 to 24 hours or preferably 2 to 12 hours. It is advantageous to previously degass the components and solvents used in the polymerization reaction and to carry out said copolymerization reaction under an inert atmosphere, for example under an atmosphere of nitrogen or argon. Copolymerization can yield clear, well-defined optical copolymers, which can be worked in the conventional way using, for example, extraction, precipitation, ultrafiltration and similar techniques.

Preferably, the polymerizable composition for preparing an intermediate copolymer comprises at least one vinyl monomer containing silicone. Examples of preferred silicone-containing vinyl monomers (that is, with a single ethylenically unsaturated group) include 3-methacryloxy propylpentamethyldisiloxane, bis (methacryloxypropyl) tetramethyldisiloxane, N- [tris (trimethylsiloxy) silylpropyl] trilamide,]] tristrimethylsilyloxysilylpropyl methacrylate (TRIS), N- [tris (trimethylsiloxy) silylpropyl] methacrylamide (TSMAA), N [tris (trimethylsiloxy) silylpropyl] acrylamide (TSAA), (3-methacryloxy-2hydroxypropyloxy) propylbis (trimethylsiloxy) methylsilane), (3-methacryloxy-2hydroxypropyloxy) propyltris (trimethylsiloxy) silane, 3-methacryloxy-2- (2-hydroxyethyl) propyloxymethyloxy (methyl) hydroxypropyl) hydroxypropyl) 2-methacryloxyethyl- (methyl-bis-trimethylsiloxy-3-propyl) silyl, vinyl carbonate containing silicone or vinyl carbamate monomers (for example, 1,3-bis [4vinyloxycarbonyloxy) but-1-yl-tetramethyl-disiloxane; 3- (trimethylsilyl), propyl vinyl carbamate, 3- (vinyloxycarbonylthio) propyl- [tris (trimethylsiloxy) silane], 3- [tris (trimethylsiloxy) silyl] propylvinyl carbamate, 3- [tris (trimethylsiloxy) silyl] carbamate] allyl propyl, 3- [tris (trimethylsiloxy) silyl] propyl vinyl carbonate, tbutyldimethylsiloxyethyl vinyl carbonate; trimethylsilyl vinyl carbonate, and trimethylsilyl vinyl carbonate). A preferred monomer containing silicone is TRIS, which is referred to as 3-methacryloxypropyltris (trimethylsiloxy) silane, and represented by CAS number 17096-07-0. The term TRIS also includes dimers of 3-methacryloxypropyltris (trimethylsiloxy) silane.

More preferably, an intermediate copolymer of the invention comprises: about 15% to about 80% by weight, preferably about 25% to about 70% of siloxane units derived from one or more siloxane-containing monomers and / or one or more macromers containing siloxane; about 10% to about 80%, preferably about 15% to 60% by weight, hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; about 1% to about 30%, preferably about 5% to about 25% of units containing silicone derived from one or more vinyl monomers containing silicone; and about 2% to about 30%, preferably about 4% to about 20% by weight of pendant hydrophilic polymer chains derived from one or more preformed hydrophilic polymers having a single ethylenically unsaturated group.

According to the invention, the ethylene functionalization of the intermediate copolymer can be carried out by covalent attachment of the ethylenically unsaturated group to the functional groups (for example, amine, hi43 droxyl, carboxyl, isocyanate, epoxy groups) of the intermediate copolymer. Any vinyl monomer having a hydroxy, amino, carboxyl, epoxy, acid chloride, isocyanate group, which is correative with the isocyanate, amine, hydroxyl, carboxy or epoxy groups of an intermediate copolymer, in the absence or presence of a coupling agent (such as, for example, EDC, diisocyanate or diacid chloride) can be used in the ethylene functionalization of the intermediate copolymer. Examples of such vinyl monomers include, without limitation, for reaction with terminal hydroxy groups, 2-isocyanatoethyl methacrylate, methacrylic anhydride, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, acryloyl chloride or methacrylyl chloride, glycidyl methacrylate; for reaction with terminal amine groups, 2-isocyanatoethyl methacrylate, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, methacrylic anhydride, acrylic acid, methacrylic acid, acrylyl chloride or methacrylyl chloride; for reaction with terminal carboxy groups in the presence of EDC, vinylamine, 2-aminoethyl methacrylate or 3-aminopropyl methacrylamide. The above list is not exhaustive but illustrative. One skilled in the art will know how to select a vinyl monomer with a functional group to ethylene-functionalize intermediate copolymers.

A prepolymer of the invention is capable of forming, preferably in the absence of any hydrophilic vinyl monomer, a silicone hydrogel or contact lens, which has a high oxygen permeability (characterized by an apparent oxygen permeability of at least 40 barrers, preferably by least about 60 barrers, even more preferably at least 80 barrers) and the hydrophilic surface (characterized by having a weighted water contact angle of less than about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less). The silicone hydrogel material or contact lens preferably has a high ion permeability (characterized by a Diffusion coefficient of lonoflux, D, greater than about 1.5 χ 10 '⁶mm²/ minute, preferably greater than about 2.6 χ 10 '⁶ mm²/ minute, more preferably greater than about 6.4 χ 10 '⁶ mm²/minute). The silicone hydrogel or contact lens material preferably has an elastic modulus of about 2.0 MPa or less, preferably about 1.5 MPa or less, more preferably about 1.2 or less, even more preferably about 0.4 MPa to about 1.0 MPa. The silicone hydrogel or contact lens material preferably has a water content preferably from about 18% to about 55%, more preferably from about 20% to about 38% by weight when fully hydrated. The water content of the silicone hydrogel contact lens can be measured according to the Bulk Technique as described in US 5,849,811.

Preferably, the prepolymers used in the invention are previously purified in a manner known per se, for example, by precipitation with organic solvents, such as, acetone, filtration and washing, extraction in an appropriate solvent, dialysis or ultrafiltration, ultrafiltration being especially preferred. Through that purification process, prepolymers can be obtained in extremely pure form, for example, in the form of concentrated solutions that are free or at least substantially free of reaction products, such as salts and starting materials, such as, for example, example, non-polymeric constituents. The preferred purification process for the prepolymers used in the process according to the invention, ultrafiltration, can be carried out in a manner known per se. It is possible that ultrafiltration is performed repeatedly, for example, two to ten times. Alternatively, ultrafiltration can be performed continuously, until the selected degree of purity is obtained. The selected degree of purity can, in principle, be as high as desired. An appropriate measure for the degree of purity is, for example, the concentration of the dissolved salts obtained as by-products, which can be determined simply in a known manner. Thus, after polymerization, the device will not need further purification, such as, for example, costly and complicated extraction of the non-polymerized matrix forming material. In addition, the crosslinking of the prepolymer can take place in the absence of the solvent or in the aqueous solution, such that the subsequent solvent exchange or hydration step is not necessary.

In another aspect, the invention provides a flexible contact lens. The flexible contact lens of the invention comprises: a silicone hydrogel material that is obtained by curing a lens forming material in a mold, wherein the lens forming material comprises an actinically crosslinkable or polymerizable prepolymer, wherein the prepolymer comprises (1) siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers; (2) hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; and (3) pendant hydrophilic polymer chains that are covalently attached to the copolymeric chain and derived from one or more preformed hydrophilic polymers each having a single crosslinkable group, wherein the pendant hydrophilic chains are free from actinically crosslinkable groups, where the preformed hydrophilic polymer has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer, but high enough to provide the flexible contact lens with an angle of contact with water of about 90 degrees or less, without surface post-curing treatment and when it is present in the prepolymer in an amount of about 2% at about 30% by weight.

According to the invention, a lens forming material is a composition that can be a solution or a melt at a temperature of about 20 ° C to about 85 ° C. Preferably, a lens forming material is a solution of at least one prepolymer of the invention and other desirable components in water or an organic solvent or a mixture of water and one or more organic solvents.

A solution of at least one prepolymer can be prepared by dissolving the prepolymer and other components in any suitable solvent known to one skilled in the art. Examples of suitable solvents are described above.

All of the various embodiments of the prepolymer of the invention described above can be employed in this aspect of the invention.

The lens forming material may optionally comprise46, but preferably, does not comprise one or more vinyl monomers and / or one or more crosslinking agents (i.e. compounds with two or more ethylenically unsaturated groups and with a molecular weight of less than 700 Daltons ). However, the quantity of these components must be so low that the final ophthalmic device does not contain unacceptable levels of unpolymerized monomers and / or crosslinking agents. The presence of unacceptable levels of unpolymerized monomers and / or crosslinking agents will require extraction to remove them, which requires additional steps that are costly and ineffective. However, preferably, the lens-forming material is substantially free of vinyl monomer and crosslinking agent (i.e., preferably about 2% or less, more preferably about 1% or less, even more preferably about 0.5% or less by weight of the combination of vinyl monomer and crosslinking agent).

It should be understood that a lens forming material may also comprise various components, such as, for example, polymerization initiators (for example, photoinitiator or thermal initiator), a dyeing agent for visibility (for example, dyes, pigments or mixtures) UV blocking agent (absorption), photosensitizers, inhibitors, antimicrobial agents (for example, preferably silver nanoparticles or stabilized silver nanoparticles), bioactive agent, leachable lubricants, fillers and the like, as known to one skilled in the art.

Initiators, for example, selected from materials well known for such use in the polymerization technique, can be included in the lens forming material in order to promote, and / or increase the rate of polymerization reaction. A primer is a chemical agent capable of initiating polymerization reactions. The initiator can be a photoinitiator or a thermal initiator.

A photoinitiator can initiate free radical polymerization and / or crosslinking using light. Suitable photoinitiators are benzoyl methyl ether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclo47 hexyl phenyl ketone and types Darocur and Irgacur, preferably Darocur 1173TM and Darocur 2959TM. Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzyldiphenylphosphine oxide; bis- (2,6-dichlorobenzoyl) -4-Npropylphenylphosphine oxide; and bis- (2,6-dichlorobenzoyl) -4-N-butylphenylphosphine oxide. Reactive photoinitiators that can be incorporated, for example into a macromer or can be used as a special monomer, are also suitable. Examples of reactive photoinitiators are those described in EP 632 329, incorporated herein in its entirety by reference. The polymerization can then be triggered by actinic radiation, for example, light, specifically UV light of an appropriate wavelength. The necessary spectra can therefore be controlled, if appropriate, by adding appropriate photosensitizers.

Examples of suitable thermal initiators include, but are not limited to 2,2'-azobis (2,4-dimethylpentanonitrile), 2,2'-azobis (2-methylpropanonitrile), 2,2'-azobis (2-methylbutanonitrile), peroxides, such as benzoyl peroxide and the like. Preferably, the thermal initiator is azobisisobutyronite (AIBN).

Examples of preferred pigments include any dye permitted in medical devices and approved by the FDA, such as Blue D&amp;C number 6, Green D&amp;C number 6, Violet D&amp;C number 2, carbazole violet, certain copper complexes, certain chromium oxides, various oxides of iron, phthalocyanine green, fitalocyanine blue, titanium dioxide, etc. See, Marmiom DM Handbook of US Colorants for a list of dyes that can be used in the present invention. A more preferred eoncretization of a pigment includes (Cl is the color index number), without limitation, for a blue color, phytoocyanin blue (pigment blue 15: 3, Cl 74160), cobalt blue (pigment blue 36, Cl 77343 ), cyan toner BG (Cyan Toner) (Clariant), blue Permajet B2G (Clariant); to a green, phthalocyanine green color (Green pigment 7, Cl 74260) and chromium sesquioxide; for yellow, red, brown and black, several iron oxides; PR122, PY154, for violet, carbazole violet; for black, black CK monolith (CIBA Specialty Chemicals).

The bioreactive agent incorporated into the polymeric matrix is ​​any compound that can prevent eye disease or reduce symptoms of eye disease. The bioreactive agent can be a drug, an amino acid (for example, taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid or any combination thereof. Examples of useful drugs include, but are not limited to, rebamipide, ketotifen, olaptidine, chromoglycolate, cyclosporine, nedocromil, levocabastine, lodoxamide, ketotifen or the pharmaceutically acceptable salt or ester thereof. Other examples of bioreactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxyl acids (for example, glycolic, lactic, malic, tartaric, mandelic and citric acids and salts thereof, etc.), linoleic acids and gamma linoleic and vitamins (for example, B5, A, B6, etc.).

Examples of leachable lubricants include, without limitation, mucin-like materials and non-cross-linkable hydrophilic polymers (i.e., without ethylenically unsaturated groups). Exemplary mucin-like materials include, without limitation, polyglycolic acid, polylactides, collagen, hyaluronic acid and gelatin.

Any hydrophilic polymers or copolymers without 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 (PVAs), polyamides, polyimides, polylactone, a lactam vinyl homopolymer, a copolymer of at least one lactam vinyl in the presence or absence of one or more vinyl comonomers, an acrylamide or methacrylamide homopolymer, an acrylamide or methacrylamide copolymer with one or more hydrophilic vinyl monomers, polyethylene oxide (ie polyethylene glycol (PEG)), a polyoxyethylene derivative, poly-NN-dimethylacrylamide, polyacrylic acid, poly 2 ethyl oxazoline, heparin polysaccharides, polysaccharides and mixtures thereof.

The molecular weight of the non-crosslinkable hydrophilic polymer is preferably from about 20,000 to about 1,500,000 Daltons, more preferably49 from about 50,000 to 1,200,000 Daltons, even more preferably from 100,000 to 1,000,000 Daltons.

According to the invention, the lens-forming material can be introduced (dispensed) into the cavity formed by a mold according to any of the known methods.

Lens molds for making contact lenses are well known to the person skilled in the art and are used, for example, in casting molding or spin casting. For example, a mold (for foundry molding) generally comprises at least two mold sections (or portions) or mold halves, i.e., first and second mold halves. The first half of the mold defines a first molding surface (or optical) and the second half of the mold defines a second molding surface (or optical). The first and second mold halves are configured to receive one another, such that a cavity for forming the lens is formed between the first molding surface and the second molding surface. The molding surface of a mold half is the cavity-forming surface of the mold and is in direct contact with the lens-forming material.

Methods for fabricating mold sections for casting a contact lens are generally well known to those skilled in the art. The process of the present invention is not limited to any specific method of forming a mold. In fact, any method for forming a mold can be used in the present invention. The first and second mold halves can be formed using various techniques, such as injection molding or lamination (lathing). Examples of suitable processes for forming the mold halves are described in US Patent No. 4,444,711 to Schad; 4,460,534 to Boehm and others; 5,843,346 to Morrill; and 5,894,002 by Boneberger et al., which are also incorporated herein by reference.

Virtually all materials known in the art for making molds can be used to make molds for preparing eye lenses. For example, polymeric materials such as polyethylene, polypropylene, polystyrene, PMMA, cyclic olefin copolymers (eg Topas® COC from Ticona GmbH in Frankfurt, Germany and Summit, New Jersey; Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY) or similar can be used. Other materials that allow transmission of UV light would be used, such as quartz, glass, CaF₂, and sapphire.

In a preferred embodiment, when the polymerizable components in the lens forming material are composed essentially of prepolymers, reusable molds can be employed. Examples of reusable molds made of quartz or glass are those described in US Patent No. 6,627,124, which are incorporated by reference in their entirety. In this regard, the lens-forming material is poured into a mold consisting of two mold halves, the two mold halves not touching each other, but having a fine annular slit arranged between them. The slot is connected to the mold cavity, so that excess lens-forming material can seep into the slot. Instead of polypropylene molds that can be used only once, it is possible to use quartz, glass or sapphire molds that are reusable, since, following the production of the lens, these molds can be quickly and effectively cleaned for removing unreacted materials and other residues, using water or an appropriate solvent that can be air dried. Reusable molds can also be manufactured from a cyclic olefin copolymer, such as, for example, Topas® COC classification 8007-S10 (clear amorphous copolymer of ethylene and norbornene) from Ticona GmbH in Frankfurt, Germany and Summit, New Jersey, Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY. Due to the ability to reuse the mold halves, a relatively high expense can be spent at the time of their production, in order to obtain extremely high precision molds and reproduction capacity. Since the mold halves do not touch the region where the lenses will be produced, that is, the cavity or faces of the actual mold, damage as a result of contact can be avoided. This guarantees a long service life of the molds, which, specifically, also ensures high reproducibility of the contact lenses to be produced and high fidelity to the lens design.

After the lens-forming material is dispensed into the mold, it is polymerized to produce the contact lens. Crosslinking can be initiated in the mold, for example, by means of actinic radiation, such as UV radiation, ionizing radiation (for example, gamma or x-ray irradiation). When the prepolymers of the invention are the polymerizable components in the lens forming material, the mold containing the lens forming material can be exposed to a spatial limitation of the actinic radiation for crosslinking the prepolymers.

The cross-linking according to the invention can be carried out in a very short time, for example, in u 60 minutes, advantageously in □ 20 minutes, preferably in □ 10 minutes, more preferably in □ 5 minutes, specific preferably in 1 to 60 seconds and more specifically in 1 to 30 seconds.

The contact lenses according to the invention can be produced from one or more radiation curable prepolymers of the invention in a very simple and efficient way, compared to the prior art. This is based on many factors. On the one hand, starting materials can be purchased or produced economically. Second, there is the advantage that prepolymers are surprisingly stable, so that they can undergo a high degree of purification. There is no practical need for subsequent purification, such as in the specific complicated extraction of nonpolymerized constituents after curing the lenses. In addition, the new polymerization method can be used to produce contact lenses with desirable mechanical and physical properties. Finally, photopolymerization is carried out within a short period of time, so that, from this point of view, also the production process for contact lenses according to the invention can be established in an extremely economical way.

The opening of the mold, so that the molded article can be removed from the mold can be carried out in a manner known per se.

If the molded contact lens is produced solvent-free from a prepolymer already purified according to the invention, then, after removing the molded lens, it is not normally necessary to carry out the purification steps, such as extraction. This is due to the fact that the prepolymers employed do not have any unwanted constituents of low molecular weight; consequently, the crosslinked product is also free or substantially free of such constituents and subsequent extraction can be dispensed with. Consequently, the contact lens can be transformed directly into the ordinary mode, by hydration, into a ready-to-use contact lens. Appropriate hydration embodiments are known to a person skilled in the art, so ready-to-use contact lenses with a wide range of water content can be obtained. The contact lens is expanded, for example, in water, in an aqueous saline solution, especially an aqueous saline solution having an osmolarity of about 200 to 450 milli-osmols in 1,000 ml (unit; mOsm / ml), preferably about 250 to 350 mOsm / L and especially about 300 mOsm / L or in a mixture of water or an aqueous saline solution with a physiologically compatible polar organic solvent, for example, glycerol. Preference is given to expansions of the article in water or in aqueous saline solutions.

If the molded contact lens is produced from an aqueous solution of an already purified prepolymer according to the invention, then the crosslinked product will also not contain any problematic impurities. Therefore, it is not necessary to perform subsequent extraction. Since the crosslinking is carried out in an essentially aqueous solution, it is additionally unnecessary to carry out subsequent hydration. The contact lenses obtained by this process are, therefore, remarkable, according to an advantageous embodiment, in that they are suitable for the intended use, without extraction. Intended use should be understood, in this context, as contact lenses that can be used in the eyes of human beings.

Similarly, if the molded contact lenses are produced from a solvent solution of a pre-polymer already purified, according to the invention, it is not necessary to perform subsequent extraction, but instead of the hydration process, replace the solvent.

Contact lenses can also be subjected to additional processes, such as, for example, surface treatment, sterilization and the like.

The contact lenses of the invention preferably have an oxygen permeability of at least about 40 barrers, more preferably at least about 60 barrers, even more preferably at least about 80 barrers. According to the invention, an oxygen permeability is an apparent oxygen permeability (measured directly when testing a sample with a thickness of about 100 microns) according to the procedures described in the Examples.

A contact lens of the invention has an elastic modulus of about 2.0 MPa or less, preferably about 1.5 MPa or less, more preferably about 1.2 or less, even more preferably about 0.4 MPa at about 1.0 MPa.

A contact lens of the invention additionally has a Lonoflux Diffusion Coefficient, D, preferably at least about

1.5 χ 10 '⁶ mm²/ minute, more preferably at least about 2.6 χ 10 '⁶mm²/ minute, even more preferably at least about 6.4 χ 10 '⁶mm²/minute.

A contact lens of the invention additionally has a water content preferably from about 15% to about 55%, more preferably from about 20% to about 38% by weight when fully hydrated. The water content of silicone hydrogel contact lenses can be measured according to the Bulk Technique as described in US 5,849,811.

A contact lens of the invention has a surface hydrophilicity characterized by having a weighted water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, more preferably about 60 degrees or less.

In a further aspect, the invention provides a method for producing flexible contact lenses. The method comprises the steps of: provision of a mold for manufacturing a flexible contact lens, wherein the mold has a first mold half with a first molding surface defining the front surface of a contact lens and a second mold half with a second mold surface defining the rear surface of the contact lens, where the first and second mold halves are configured to receive each other, such that a cavity is formed between said first and second mold surfaces; introducing the lens forming material into the cavity, wherein the lens forming material comprises one or more actinically crosslinkable prepolymers and is substantially free of vinyl monomer and / or crosslinking agent, wherein each of one or more prepolymers comprises (1) siloxane units derived from one or more siloxane-containing monomers and / or one or more siloxane-containing macromers; (2) hydrophilic units derived from one or more hydrophilic monomers and / or one or more hydrophilic macromers; and (3) pendant hydrophilic polymer chains that are covalently attached to the copolymeric chain and derived from one or more preformed hydrophilic polymers each having a single crosslinkable group, wherein the pendant hydrophilic chains are free from actinically crosslinkable groups, where the preformed hydrophilic polymer has a molecular weight low enough to be efficient and covalently incorporated into the prepolymer, but high enough to provide the flexible contact lens with a water contact angle of about 90 degrees or less, with no surface post-cure treatment when it is present in the prepolymer in an amount of about 2% about 30% by weight; and actinic irradiation of the composition in the mold to crosslink said one or more crosslinkable prepolymers to form the contact lens.

All of the various embodiments of the prepolymer and contact lenses of the invention described above can be employed in this aspect of the invention.

The foregoing disclosure will allow one skilled in the art to practice the invention. In order to allow the reader a better understanding of the specific embodiments and advantages of the same, reference is suggested to the following non-limiting examples. However, the following examples should not be read as limiting the scope of the invention.

Example 1

Surface Hydrophilicity Tests (wetting capacity)

The angle of contact with water over a contact lens is a general measure of the surface hydrophilicity (or wetting capacity) of the contact lens. Specifically, a low contact angle with water corresponds to a more hydrophilic surface. Mean contact angles (lead) of contact lenses are measured using the Wilhelmy Plate method.

Coating Integrity Tests

The integrity of a coating on the surface of a contact lens can be tested according to the following Sudan Black staining test. Contact lenses with a coating (for example, an LbL coating, a plasma coating or any other coatings) are immersed in Sudan Black dye solution (Sudan Black in vitamin Ε oil). The Sudan Black dye is hydrophobic and has a greater tendency to be absorbed by a hydrophobic material or on a hydrophobic lens surface or hydrophobic stains on a partially coated surface of a hydrophobic lens (for example, silicone hydrogel contact lens). If the coating on a hydrophobic lens is intact, no colored spots will be seen on or on the lens. All test lenses are fully hydrated.

Coating Durability Tests

The lenses are digitally rubberized 30 times with Aquify® all-purpose lens care solution and then rinsed with Softwear® saline solution. The digitally rubberized lenses are then soaked in the Softwear® saline solution for 30 minutes. The above procedure is repeated for predetermined times, for example, from 1 to 30 times, (ie, number of consecutive digital rubber tests that mimic cleaning and soaking cycles). The lenses are then subjected to the Sudan Black test (ie, coating integrity test described above) to examine whether the coating is still intact. In order to survive the digital rubber test, there is no significant increase in coloring spots (for example, coloring spots cover no more than 5% of the total lens surface).

Measurements of oxygen permeability.

The oxygen permeability of a lens and the oxygen carrying capacity of a lens material are determined according to a technique similar to that described in US Patent No. 5,760,100 and in an article by Winterton et al., (The Cornea: Transactions of the World Congress on the Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pages 273-280), both of which are incorporated herein in their entirety by reference. Oxygen flows (J) are measured at 34 ° C in a wet cell (ie gas streams are maintained at 100% relative humidity) using a Dk1000 instrument (available from Applied Design and Development Co., Norcross, GA) or similar analytical instrument. An air stream, having a known percentage of oxygen (for example, 21%), is passed through one side of the lens at a rate of about 10 to 20 cm³/ minute, while a stream of nitrogen is passed on the opposite side of the lens at a rate of about 10 to 20 cm³/minute. A sample is equilibrated in the test medium (ie, saline or distilled water) at the prescribed test temperature for at least 30 minutes before measurement, but for no more than 45 minutes. Any test medium used as the overcoat is balanced at the prescribed test temperature for at least 30 minutes before measurement, but for no more than 45 minutes. The speed of the agitation motor is set to 1,200 ± 50 rpm, corresponding to an indicated setting of 400 ± 15 on the stepped motor controller57. The barometric pressure, Pmeasured, surrounding the system is measured. The thickness (t) of the lens in the area being exposed to the test is determined by measuring around 10 locations with a VL-50 Mitotoya micrometer or similar instrument and weighing the measurements. The concentration of oxygen in the nitrogen stream (that is, the oxygen that diffuses through the lens) is measured using the DK1000 instrument. The apparent oxygen permeability of the lens material, Dk_ap, is determined from the following formula:

Dkap = Jt / (P oxygen) where J = oxygen flow [microliters O₂ / cm²-minute]

P oxygen ^— (P measure ^— P water vapor) = (% O2 in the air stream) [mm Hg] = partial pressure of oxygen in the air stream

Pmeasure = barometric pressure (mm Hg)

Water vapor - 0 mm Hg at 34 ° C (in a dry cell) (mm Hg)

P vapor of water = 40 mm Hg at 34 ° C (in a wet cell) (mm Hg) t = average lens thickness in relation to the exposed test area (mm) where Dkgp is expressed in units of barrers. The oxygen transmission capacity (Dk / t) of the material can be calculated by dividing the oxygen permeability (Dk_ap) by the average thickness (t) of the lenses.

Ion permeability measurements. The permeability of the ion of a lens is measured according to the procedures described in US Patent number 5,760,100 (incorporated in this document in its entirety by reference). The ion permeability values ​​reported in the following examples are in relation to the Lonoflux Diffusion Coefficients (D / D_ref) with reference to a lens material, Alsacon, as a reference material. Alsacon has a lonoflux Diffusion Coefficient of 0.314 x 10 '³ mm²/minute.

Example 2A

Synthesis of the Intermediate Copolymer (YS-3203-028-1)

A mixture of 60.0 g of □, Z-bisacrylamide-polydimethylsiloxane mw r 11,500, θ 241.6 g of 1-propanol is added to the 2 liter caged heating / cooling reaction vessel, equipped with a mechanical stirrer, condenser, vacuum connection / N₂ and thermostat. The solution is cooled to 8 ° C and degassed for 3 evacuation cycles at 1.5 kPa (15 mbar) for 15 minutes and flushed with N₂. The system is controlled under a nitrogen environment until the end of the reaction. The monomeric solution containing 25.83 g of Ν, Ν-dimethyl acrylamide, 11.07 g of PEG acrylate (MM = 454), 1.05 g of cysteamine hydrochloride and 140 g of 1-propanol is added slowly to the container reaction by an LC pump connected to a degassing unit. The rate of addition of the monomeric solution is controlled at 3.0 mL / minute. After all monomeric solution is added, the mixture is slowly heated from 8 ° C to 68 ° C over a period of time of one hour. When the polymerization temperature reaches 68 ° C, the starter solution which was composed of 0.1 g of AIBN and 40.0 g of 1-propanol (degassed for 3 evacuation cycles to 8 kPa (80 mBar) for 5 minutes and flowed with N₂), was injected into the reaction mixture. The feed solution that contains

1.95 g of cysteamine hydrochloride and 198.4 g of 1-propanol is added to the reaction mixture for 2 hours through an LC pump connected to a degassing unit. The rate of addition of this feed solution is controlled at □ 2.5 mL / minute. After all the feed solution is added, the polymerization is carried out at 68 ° C for an additional 6 hours.

After the reaction mixture is cooled to room temperature, the reaction solvent, 1-propanol is gradually replaced with deionized water in the rotoevaporator until the mixture turns into an aqueous emulsion. The emulsion is purified by ultrafiltration using a 10 KD molecular weight cut membrane. The yield of the intermediate copolymer is 70%.

Example 2B

Prepolymer synthesis

The purified emulsion solution of Example 2A was diluted to Li 2 L and then loaded into a 2 liter heated / cooled reaction container equipped with a mechanical stirrer and thermometer. A buffered salt, 4.0 g of NaHCOs is added and then the mixture is cooled to 0 ° C. The pH of the solution is adjusted to 9.5 with NaOH (aq._Uoso) 20% and then starting the addition of 5.8 ml of acryloyl chloride for a period of 2 hours followed by another hour of stirring. The pH of the solution is controlled to 9.5 during the acrylation by a static pH control equipment with NaOH (_aq) to 20%. After the reaction is complete, the pH of the solution is adjusted to 7.0 with HCI &lt;_aq) at 2N and then purified by ultrafiltration using a 10 KD cut molecular weight membrane. The purified emulsion is freeze-dried and yielded a white solid. Example 2C

Lens Formulation and Manufacturing

The prepolymer obtained in Example 2B is dissolved in a solvent, 1-propanol. The solution is filtered under pressure through a 0.45 µm filter, followed by the first concentration stage at about 30% solid. After the solid content needs to be verified, 0.25% by weight of DarocurL 2959 (based on the macromonomer content) is added followed by additional concentration until the final percentage of solids is 60%. The viscosity of the formula and curing time is measured by photoreology.

The formula is centrifuged at 5,000 rpm for 10 minutes to remove bubbles.

The formula is cast in polypropylene molds and cured by UV light at an intensity of 2.05 mW / cm² at 310 nm with the curing time providing equivalent total energy obtained from photoreology measurement.

Example 3A

Synthesis of intermediate copolymer (YS-3203-028-2)

The intermediate copolymer is prepared in the same manner as in Example 2A, except that 1) the monomeric solution is composed of 26.215 g of Ν, Ν, -dimethyl acrylamide, 11.24 g of PEG-Acrylate (MM = 454), 0, 84 g of cysteamine hydrochloride, 2) the starter solution being composed of 0.15 g of AIBN and 40.0 g of 1-propanol, and 3) the feed solution is composed of 1.56 g of cysteamine hydrochloride and 198.4 g of 1-propanol. The copolymer yield is 60%.

Example 3B

Prepolymer synthesis

Acrylation of the intermediate copolymer prepared in Example 3A is carried out according to the procedure described in Example 2B except that 4.7 ml of acryloyl chloride are employed. After the emulsion solution is purified and lyophilized, the final product is a white solid. Example 3C

Lens formulation and manufacturing

The prepolymer obtained in Example 3B is formulated and then the lenses are produced according to the procedure described in Example

2C.

Example 4

The lenses prepared in Examples 2C and 3C are immersed in a solution of PAA (polyacrylic acid). All lenses after being treated with PAA solution are transparent and show the desired mechanical properties, ion permeability and oxygen permeability (See lens properties in Table 1, appropriate methods for determining ion permeability and oxygen permeability are described in example 1).

<td colspan="4">Lens characterization</td>

<td rowspan="6">properties</td><td>Lot number</td><td>Example 2C</td><td>Example 3C</td>

<td>Module E, MPa</td><td> 0,73</td><td> 0,66</td>

<td>EtB%</td><td> 285%</td><td> 295%</td>

<td>H₂O%</td><td> 17,1%</td><td> 22,4%</td>

<td>Dk</td><td> 106</td><td> 178</td>

<td>IP</td><td> 1,6</td><td> 5,7</td>