BRPI0620192A2 - methods and systems for leaching and releasing hydrogel ophthalmic lenses with alcohol solutions - Google Patents

Abstract

METHODS AND SYSTEMS FOR LEACHING AND RELEASE OF OPHTHALMIC HYDROGEL LENSES WITH ALCOHOL SOLUTIONS. The present invention relates to methods and systems for processing hydrogel lenses using aqueous solutions as leaching aids and as release aids.

Description

Report of the Invention Patent for "METHODS AND SYSTEMS FOR LIXIVIATION AND RELEASE OF HYDROGEL Ophthalmic Lenses With ALCOHOL SOLUTIONS".

FIELD OF INVENTION

The present invention relates to a process for producing ophthalmic lens made of silicone hydrogels. More specifically, the present invention relates to methods and systems for leaching of ophthalmic lens components and releasing mold part lenses where they have been formed.

BACKGROUND OF THE INVENTION

It is well known that contact lenses can be used to improve vision. Various contact lenses have been commercially produced for many years. Early models of contact lenses were made of hard materials. Although these lenses are still currently used in some applications, they are not suitable for all patients due to their poor comfort and relatively low oxygen permeability. Later developments in the field gave rise to soft hydrogel-based contact lenses.

Hydrogel contact lenses are very popular today. These lenses are often more comfortable to wear than contact lenses made of hard materials. Soft soft contact lenses can be manufactured by forming a lens in a multipart mold where the combined parts form a topography consistent with the desired end lens.

Multipart molds used to shape hydrogels in a useful article, such as an ophthalmic lens, may include, for example, a first mold portion with a convex surface that corresponds to the back curve of an ophthalmic lens and a second mold portion with a concave surface that corresponds to a frontal curve of the ophthalmic lens. To prepare a lens using such mold portions, an uncured hydrogel lens formulation is placed between the concave and convex surfaces of the mold portions and subsequently cured. The hydrogel lens formulation may be cured, for example, by exposure to either or both heat and light. The cured hydrogel forms a lens according to the dimensions of the mold portions.

Following curing, traditional practice dictates that the mold portions are separated and the lens remains attached to one of the mold portions. A release process loosens the lens from the remaining mold portion. The extraction step removes unreacted components and diluents (hereinafter referred to as "UCDs") from the lens and affects the clinical viability of the lens. If UCDs are not extracted from the lens, they can make the lens uncomfortable to use.

According to the prior art, lens release from the mold can be facilitated by exposing the lens to aqueous or saline solutions that act to swell the lens and decrease lens adhesion to the mold. Exposure to aqueous or saline solution may additionally serve to extract UCDs and thus make the lens more comfortable to use and clinically acceptable.

New developments in the field have led to contact lenses that are made of silicone hydrogels. Known hydration processes using aqueous solutions to perform release and extraction have not been effective with silicone hydrogel lenses. Consequently, attempts have been made to release silicone lenses and remove UCDs using organic solvents. Processes have been described where a lens is immersed in an alcohol (ROH), ketone (RCOR '), aldehyde (RCHO), ester (RCOOR'), amide (RCONR'R ") or N-alkyl pyrrolidone for 20 hours-40 hours and in the absence of water, or in a mixture with water as a minor component (see, for example, US Patent No. 5,258,490).

However, while some success has been achieved with known processes, the use of highly concentrated organic solutions can present drawbacks, including, for example: safety risk; high risk of downtime for a manufacturing line; high cost of release solution; and the possibility of collateral damage due to the explosion.

Thus, it would be advantageous to find a method of producing a silicone hydrogel contact lens that requires the use of little or no organic solvent, avoids the use of flammable agents, which effectively releases lenses from the molds where they were formed and remove UCDs from the lens.

SUMMARY OF THE INVENTION

Thus, the present invention provides methods of leaching a silicone hydrogel ophthalmic lens from UCDs without soaking the lens in organic solvents. According to the present invention, release of a silicone hydrogel lens from a mold where the lens is formed is facilitated by exposing the lens to an aqueous solution of an effective amount of a release aid. In addition, lens UCD leaching is also facilitated by exposing the lens to an aqueous solution of an effective amount of a leaching aid.

Further, the present invention generally relates to ophthalmic lenses made of materials including wetting silicone hydrogels formed from a reaction mixture including at least one high molecular weight hydrophilic polymer and at least one funnel-silicone-containing monomer. hydroxylated. In some embodiments, ophthalmic lenses are formed from a reaction mixture including a high molecular weight hydrophilic polymer and an effective amount of a hydroxyl functionalized silicone containing monomer.

In other embodiments, the present invention relates to a method for preparing an ophthalmic lens that includes mixing a high molecular weight hydrophilic polymer and an effective amount of a hydroxyl functionalized silicone containing monomer to form a transparent solution and cure of said solution. Some embodiments may then include one or more of (a) a mixture of a high molecular weight hydrophilic polymer and an effective amount of a hydroxyl functionalized silicone-containing monomer; and (b) curing the product of step (a) to form a biomedical device and curing the product of step (a) to form a humidifying biomedical device.

In some embodiments, the present invention further relates to an ophthalmic lens formed from a reaction mixture comprising at least one hydroxyl functionalized silicone-containing monomer and an amount of high molecular weight hydrophilic polymer sufficient to incorporate into the lens without a surface treatment, an advanced contact angle of less than about 80 degrees.

DETAILED DESCRIPTION OF THE INVENTION

It has been found that a silicone hydrogel ophthalmic lens can be released from a mold where it has been cured by exposing the cured lens to an aqueous solution of an effective amount of a release aid. It has also been found that adequate removal of Leachable Materials from the silicone hydrogel ophthalmic lens can be accomplished by exposing the cured lens to an aqueous solution of an effective amount of a leaching aid.

Definitions

As used herein, "proper removal of Leachable Materials" means that at least 50% of the Leachable Materials have been removed from a lens after lens treatment.

As used herein, "Leachable Material" includes UCDs and other material that is not polymer bound and may be extracted from the polymer matrix, for example, by leaching with water or an organic solvent.

As used herein, a "Leaching Aid" is any compound that if used in an effective amount in an aqueous solution to treat an ophthalmic lens can provide a lens with an adequate amount of Leaching Material removal.

As used herein the term "monomer" is a compound having at least one polymerizable group and an average molecular weight of about less than 2000 Daltons, as measured by refractive index detection by gel permeation chromatography. Thus, monomers may include dimers and in some cases oligomers, including oligomers made of more than one monomer unit.

As used herein, the term "Ophthalmic Lens" refers to devices residing in or above the eye. Such devices may provide optical correction, wound care, drug delivery, diagnostic functionality, enhancement or cosmetic effect or a combination of these properties. The term lens includes, but is not limited to, soft contact lenses, hard contact lenses, intraocular lenses, coating lenses, eye inserts, and optical inserts.

As used herein, a "release aid" is a compound or mixture of compounds, excluding organic solvents, which, when combined with water, decreases the time required to release an ophthalmic lens from a mold as compared to time. required for the Freeze of such a lens using an aqueous solution that does not comprise the release aid.

As used herein, "release of a mold" means that a lens is either completely detached from the mold, or just loosely attached so that it can be removed with light shaking or loosened with a "swab".

As used herein, the term "treating" means exposing a cured lens to an aqueous solution including at least one of: a leaching aid and a release aid.

As used herein and also as defined above, the term "UCD" means unreacted components and diluents. Treatment

In accordance with the present invention, treatment may include exposing a cured lens to an aqueous solution comprising at least one of: a leaching aid and a release aid. In many ways, treatment may be performed, for example, by immersing the lens in a solution or exposing the lens to a solution stream. In various embodiments, treatment may also include, for example, one or more of: heating the solution; stirring of the solution; increasing the release aid level in the solution to a level sufficient to cause lens release; mechanical lens shaking; and increasing the level of leaching aid in the solution to a level sufficient to facilitate proper removal of UCDs from the lens. By way of non-limiting examples, various implementations may include UCD release and removal that are performed by a batch process where lenses are submerged in a solution contained in a fixed tank for a specified period of time or in a vertical process where the lens is exposed to a continuous flow of a solution that includes at least one of a leaching aid and a release aid.

In some embodiments, the solution may be heated with a heat exchanger or other heating apparatus to further facilitate lens leaching and lens release from a portion of the mold. For example, heating may include raising the temperature of an aqueous solution to a boiling point while a hydrogel lens or part of the mold to which the lens is adhered is submerged in the heated aqueous solution. Other embodiments may include controlled cyclization of the temperature of the aqueous solution.

Some modalities may also include the application of physical agitation to facilitate leaching and release. For example, the portion of the lens mold to which the lens is attached may be vibrated or moved back and forth within an aqueous solution. Other embodiments may include ultrasonic waves through the aqueous solution.

These and other similar processes may provide an acceptable means of lens release and removal of lens UCDs prior to packaging.

Release

In accordance with the present invention, release of a silicone hydrogel lens is facilitated by treating the lens with a solution including one or more release aids combined with water at effective concentrations to cause release of the lens. In some embodiments, release may be facilitated by the release solution by causing a silicone hydrogel lens to swell by 10% or more where the swelling percentage is equal to 100 times the diameter of the lens in a helper solution. lens release / diameter in borate buffered saline.

In some embodiments, the release aid may include alcohols, such as, for example, C5 to C7 alcohols. Some embodiments may also include alcohols that are useful as release aids and include primary, secondary and tertiary alcohols of one to 9 carbons. Examples of such alcohols include methanol, ethanol, n-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 2-methyl-1-butanol tert-amyl alcohol, neopentyl alcohol, 1-hexanol, 2-hexanol, 3-hexanol, 2-methyl-1-pentanol, 3-methyl-1-pentanol, 4-methyl-1-pentanol, 2-methyl-2 pentanol, 3-methyl-2-pentanol, 3-methyl-3-pentanol, 1-heptanol, 2-heptanol, 3-heptanol, 4-heptanol, 1-octanol, 2-octanol, 1-nonanol and 2-nonanol . In some embodiments, phenols may also be used.

Also, in some embodiments of the present invention Leaching Aids, which are discussed below, may also be combined with alcohols to improve the release rate. In some cases leaching aids may be used as release aids without the addition of alcohols. For example, leaching aids in concentrations greater than about 12%, or when used to release lenses with water soluble diluents such as t-amyl alcohol.

Lens materials

Ophthalmic lenses suitable for use with the present invention include those made of silicone hydrogels. Silicone hydrogels offer benefits to ophthalmic lens wearers compared to conventional hydrogels. For example, they typically offer much higher oxygen permeability, Dk1 or oxygen oxygen / transmissibility, Dk / I, where I is the thickness of the lens. Such lenses cause reduced corneal swelling due to reduced hypoxia and may cause less limb redness, improved comfort and have a reduced risk of adverse responses such as bacterial infections. Silicone hydrogels are typically made by combining silicone containing monomers or macromers with hydrophilic monomers or macromers.

Examples of silicone-containing monomers include SiGMA (2-propenoic acid, 2-methyl-, 2-hydroxy-3- [3- [1,3,3,3-tetramethyl-1 - [(trimethylsilyl) oxide) ester ] disyloxanyl] propoxy] propyl), α, ω-bismethacryloxypropylpolidimethylsiloxane, mPDMS (monomethacryloxypropyl terminated polydimethylsiloxane) and TRIS (3-methacryloxypropyltris (trimethylsiloxy)).

Examples of hydrophilic monomers include HEMA (2-hydroxyethyl methacrylate), DMA (α, β-dimethylacrylamide) and NVP (N-vinylpyrrolidone).

In some embodiments, high molecular weight polymers may be added to monomer mixtures and serve the function of internal wetting agents. Some embodiments may also include additional components or additives, which are generally known in the art. Additives may include, for example: ultraviolet absorption compounds and monomer, reactive dyes, antimicrobial compounds, pigments, photochromes, release agents, combinations thereof and the like.

Silicone monomers and macromers are mixed with hydrophilic monomers or macromers, placed in ophthalmic lens molds and cured by exposing the monomer to one or more conditions capable of causing monomer polymerization. Such conditions may include, for example: heat and light, wherein the light may include one or more of: visible light, ionization, actinic, x-ray, electron beam or ultraviolet (hereinafter "UV"). In some embodiments, the light used to cause polymerization may have a wavelength of about 250 to about 700 nm. Suitable sources of radiation include UV lamps, fluorescent lamps, incandescent lamps, mercury vapor lamps and sunlight. In embodiments, where a UV-absorbing compound is included in the monomer composition (e.g., as a UV blocker), curing may be conducted by means other than UV irradiation (such as, for example, through visible light or heat).

In some embodiments, a radiation source, used to facilitate curing, may be selected from UVA (about 315 - about 400 nm), UVB (about 280 - about 315) or visible light (about 400 - about 400 nm). 450 nm) at low intensity. Some embodiments may also include a reaction wherein the mixture includes a UV absorbing compound.

In some embodiments, where lenses are cured using heat then a thermal initiator may be added to the monomer mixture. Such initiators may include one or more of: peroxides such as benzoyl peroxide and azo compounds such as AIBN (azobisisobutyronitrile).

In some embodiments, lenses may be cured using UV or visible light and a photoinitiator may be added to the monomer mixture. Such photoinitiators may include, for example, aromatic alpha-hydroxy ketones, alkoxyoxybenzoines, acetophenones, acyl phosphine and tertiary amine oxides plus a diketone, mixtures thereof and the like. Illustrative examples of photoinitiators are 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenylpropan-1-one, bis (2,6-dimethoxybenzoyl) -2,4,4-trimethylpentyl phosphine oxide (DMBAPO ), bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and 2,4,6-trimethylbenzoyl diphenylphosphine oxide, methyl ester of benzoin and a combination of camphorquinone and ethyl 4- (N, N-dimethylamino) benzoate. Commercially available visible light primer systems include Irgacure 819, Irgacure 1700, Irgacure 1800, Irgacure 819, Irgacure 1850 (all from Ciba Specialty Chemicals) and Lucirin TPO primer (available from BASF). Commercially available UV photoinitiators include Darocur 1173 and Darocur 2959 (Ciba Specialty Chemicals).

In some embodiments, it may also be useful to include diluents in the monomer mixture, for example to improve the solubility of the various components or to increase the clarity or degree of polymerization of the polymer to be formed. Modalities may include secondary and tertiary alcohols as diluents.

Several processes are known for processing the reaction mixture in the production of ophthalmic lenses, including known rotary molding and static molding. In some embodiments, a method for producing an ophthalmic lens from a polymer includes molding silicone hydrogels. Silicone hydrogel molding can be efficient and provide precise control over the final shape of a hydrated lens. Molding an ophthalmic lens from a silicon hydrogel may include placing a metered amount of monomer mixture into a concave mold portion. A convex mold portion is then placed on top of the monomer and pressed to close and form a cavity defining a contact lens shape. The monomer mixture within the mold parts is cured to form a contact lens. As used herein, curing of the monomer mixture includes a process or condition that permits or facilitates polymerization of the monomer mixture. Examples of conditions that facilitate polymerization include one or more of: light exposure and application of thermal energy.

When the mold halves are separated then the lens typically adheres to one or the other half of the mold. It is typically difficult to physically remove the lens from this half of the mold, and it is generally preferred to place this half of the mold in a solvent to release the lens. Lens swelling that results when the lens absorbs some of this solvent typically facilitates the release of the lens from the mold.

Silicone hydrogel lenses may be made using relatively hydrophobic diluents such as 3,7-dimethyl-3-octanol. If they attempt to release such lenses in water, such diluents prevent water absorption, and do not allow sufficient swelling to cause the lens to release.

Alternatively, silicone hydrogels may be made using relatively hydrophilic and water-soluble diluents such as ethanol, t-butanol or t-amyl alcohol. When such diluents are used and the lens and mold are placed in water, the diluent may more easily dissolve and the lens may more easily release into water than if more hydrophobic diluents were used. Leachable Material

After a lens is cured the formed polymer typically contains some amount of material that is not attached to or incorporated into the polymer. Non-polymer bound leachable material may be extracted from the polymer matrix, for example by leaking with water or an organic solvent (hereinafter "Leachable Material"). Such leachable material may not be conducive to wearing the contact lens in one eye. For example, Leachable Material may slowly be released from a contact lens when the contact lens is worn on one eye and may cause irritation or a toxic effect on the wearer's eye. In some cases, Leachable Material may also appear on the surface of a contact lens where it may form a hydrophobic surface and may attract tear debris or may interfere with lens wetting.

Some material may be physically trapped in the polymer matrix and may not be able to be removed, for example by extracting with water or an organic solvent. As used herein, bonded material is not considered a Leachable Material.

Leachable material typically includes most or all of the material included in the monomer blend that has no polymerizable functionality. For example, a diluent may be a Leachable Material. Leachable material may also include nonpolymerizable impurities that were present in the monomer. As polymerization nears its end, the polymerization rate will typically decrease and a small amount of the monomer may never polymerize. Monomer that never polymerizes can be included in the material that will be leached from the polymerized lens. Leachable material may also include small polymer fragments, or oligomers. Oligomers can result from early termination reactions in the formation of any given polymer chain. Accordingly, Leachable Materials may include any or all of a mixture of the above-described components, which may vary from one another in their properties such as toxicity, molecular weight or water solubility.

Leaching Aids

According to the present invention, leaching of a silicone hydrogel lens is facilitated by exposing the lens to a solution including one or more water-combined leaching aids in effective concentrations to remove UCDs from the lens.

For example, in some embodiments, ophthalmic lenses may be subjected to treatment by exposing the lens to a leaching aid and a GC Mass Spectrometer may be used to measure the level of one or more UCDs in the ophthalmic lens. The GC Mass Spectrometer can determine if treatment with a particular leaching aid is effective in reducing a particular amount of UCDs present in the lens to a maximum threshold amount.

Thus, in some embodiments, a GC Mass Spectrometer may be used to check a maximum threshold of UCDs1 such as SiMMA1 mPDMS, SiMMA glycol, and epoxide, of approximately 300 ppm. A minimum hydration treatment time required to reduce the presence of such UCDs to 300 ppm or less in specific lenses can be determined by periodic measurements. In additional embodiments, other UCDs, such as, for example, D30 or other diluents, may be measured to detect the presence of a maximum amount of approximately 60 ppm. Modalities may also include adjusting a threshold amount of a particular UCD to the minimum detection level determinable by the test equipment.

Examples of leaching aids according to the present invention include: ethoxylated alcohols or ethoxylated carboxylic acids, ethoxylated glycosides or sugars, optionally with attached C8 to C14 carbon chains, polyalkylene oxides, sulfates, carboxylates or amine oxides of C8-C10 compounds. Examples include cocoamidopropylamine oxide, ethoxylated C12-14 fatty alcohol with 10 ethylene oxides, polyoxyethylene-2-ethylhexyl ether, polypropylene glycol, polyethylene glycol monomethyl ether, ethoxylated methyl glycoside dioleate and n-sodium salt. -octylsulfate, sodium salt of ethylhexyl sulfate.

In order to illustrate the invention the following examples are included. These examples do not limit the invention. They are only meant to suggest a method of practicing the invention. Those skilled in contact lenses, as well as other techniques, may find other methods of practicing the invention, such methods being considered to be within the scope of the present invention.

High Molecular Weight Hydrophilic Polymer As used herein "high molecular weight hydrophilic polymer" refers to substances having a weight average molecular weight of not less than about 100,000 Daltons, wherein said substances upon incorporation Silicone hydrogel formulations increase the wetting capacity of cured silicone hydrogels. The weight average molecular weight of such high molecular weight hydrophilic polymers is greater than about 150,000; more preferably from about 150,000 to about 2,000,000 Daltons, more preferably from about 300,000 to about 1,800,000 Daltons, more preferably from about 500,000 to about 1,500,000 Daltons.

Alternatively, the molecular weight of the hydrophilic polymers of the invention may also be expressed by the K value based on kinematic viscosity measurements as described in Encyclopedia of Polymer Science and Engineering, N-Vinyl Amide Polymers, Second Edition, Vol. 17, pages 198-257, John Wiley & Sons, Inc. When expressed in this manner, hydrophilic monomers having K-values of more than about 46 and preferably between about 46 and about 150. High molecular weight hydrophilic polymers are present. formulations of such devices in an amount sufficient to provide contact lenses, which without surface modification remain substantially free of surface deposition during use. Periods of use include at least about 8 hours, preferably used for several consecutive days, and most preferably for 24 hours or more without removal. Substantially free of surface deposition means that when viewed with a slit lamp at least about 70% and preferably at least about 80%, and more preferably about 90% of the lenses used in the patient population. show depositions taxed as none or light during the period of use.

Suitable amounts of high molecular weight hydrophilic polymer include from about 1 to about 15 weight percent, more preferably about 3 to about 15 percent, more preferably about 5 to about 12 percent. percent, all based on the total of all reactive components.

Examples of high molecular weight hydrophilic polymers include, but are not limited to, functionalized polyamides, polylactones, polyimides, polylactams and polyamides, polylactones, polyimides, polylactams, such as DMA functionalized by copolymerizing DMA with a lesser amount. molar of a hydroxyl-functional monomer such as HEMA, and then reacting the hydroxyl groups of the resulting copolymer with materials containing radical polymerizable groups, such as isocyanatoethylmethylcrylate or methacryloyl chloride. Hydrophilic prepolymers made of DMA or n-vinyl pyrrolidone with glycidyl methacrylate may also be used. The glycidyl methacrylate ring may be opened to give a diol which may be used in conjunction with another hydrophilic prepolymer in a mixed system to enhance compatibility of the high molecular weight hydrophilic polymer, hydroxyl functionalized silicone containing monomer and any other groups that offer compatibility. Preferred high molecular weight hydrophilic polymers are those containing a cyclic moiety in their backbone, more preferably a cyclic amide or cyclic imide. High molecular weight hydrophilic polymers include, but are not limited to, poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl -2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N -vinyl-3-ethyl-2-pyrrolidone and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-NN-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2 -ethyl oxazoline, heparin polysaccharides, polysaccharides, mixtures and their copolymers (including block or random, branched, multi-chain, comb-shaped or star-shaped) where poly-N-vinylpyrrolidone (PVP) is particularly Preferred. Copolymers may also be used as PVP graft copolymers.

High molecular weight hydrophilic polymers provide improved wetting capacity, and particularly improved in vivo wetting ability to the medical devices of the present invention. Without being bound by any theory, high molecular weight hydrophilic polymers are believed to be hydrogen bonding receptors which in aqueous environments, hydrogen bonding to water, then become effectively more hydrophilic. The absence of water facilitates the incorporation of hydrophilic polymer into the reaction mixture. Apart from specifically called high molecular weight hydrophilic polymers, it is expected that any high molecular weight polymer will be useful in the present invention as long as when said polymer is added to a silicone hydrogel formulation, the hydrophilic polymer (a) is not substantially phase separate from the reaction mixture and (b) give wetting ability of the resulting cured polymer. In some embodiments, it is preferred that the high molecular weight hydrophilic polymer be soluble in the diluent at processing temperatures. Manufacturing processes using water or water soluble diluents may be preferred because of their simplicity and reduced cost. In such embodiments, high molecular weight hydrophilic polymers that are water soluble at processing temperatures are preferred.

Hydroxyl Functionalized Silicone Containing Monomer

As used herein a "hydroxyl functionalized silicone-containing monomer" is a compound containing at least one settable group having an average molecular weight of about less than 5000 Daltons as measured by gel permeation chromatography, detection of refractive index, and preferably less than about 3000 Daltons, which is capable of compatibilizing the silicone containing monomers included in the hydrogel formulation with the hydrophilic polymer. Hydroxyl functionality is very efficient in improving hydrophilic compatibility. Thus, in a preferred embodiment, hydroxyl-functionalized silicone-containing monomers of the present invention comprise at least one hydroxyl group and at least one "-Si-O-Si" group. It is preferred that the silicone and its bound oxygen be responsible for more than about 10 weight percent of said hydroxyl functionalized silicone-containing monomer, more preferably more than about 20 weight percent.

The Si to OH ratio in the hydroxyl-functionalized silicone-containing monomer is also important to provide a hydroxyl-functionalized silicone-containing monomer that will provide the desired degree of compatibility. If the hydrophobic portion to OH ratio is too high, the hydroxyl-functionalized silicone-containing monomer may be poor in the compatibility of the hydrophilic polymer, resulting in incompatible reaction mixtures. Thus, in some embodiments, the Si to OH ratio is less than about 15: 1 and preferably from about 1: 1 to about 10: 1. In some embodiments, primary alcohols provided improved compatibility compared to secondary alcohols. Those skilled in the art will understand that the amount and selection of hydroxyl functionalized silicone containing monomer will depend on how much hydrophilic polymer is required to achieve the desired wetting capacity and the degree to which the silicone containing monomer is incompatible with the polymer. hydrophilic.

In some embodiments, the reaction mixtures of the present invention may include more than one hydroxyl-functional silicone-containing monomer. For monofunctional hydroxyl functionalized silicone-containing monomer, the preferred R1 is hydrogen, and the preferred R2, R3 and R4 are C1-6alkyl and C1-6alkylsiloxy, more preferably methyl and trimethylsilyl. For multifunctional (difunctional or higher) R1-R4 independently comprises ethylenically unsaturated polymerizable groups and more preferably comprises an acrylate, a styryl, a C1-6 alkylacrylate, acrylamide, C1-6 alkylacrylamide, N-vinylactam, N-vinylamide , C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthyl or C 2-6 alkenylphenylC 1-6 alkyl. In some embodiments, R 5 is hydroxyl, -CH 2 OH or CH 2 CHOHCH 2 OH.

In some other embodiments, R 6 is divalent C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkyloxyC 1-6 alkyl, phenylene, naphthalene, C 1-12 cycloalkyl, C 1-6 alkoxycarbonyl, amide, carboxy, C 1-6 alkylcarbonyl, carbonyl, C 1-6 alkoxy Substituted C1-6 alkyl, substituted C1-6 alkyloxy, C1-6 alkyloxy substituted C1-6 alkyl, substituted phenylene, substituted naphthalene, substituted C1-12 cycloalkyl, where substituents are selected from one or more members of the group consisting of C1-6 6 alkoxycarbonyl, C1-6alkyl, C1-6alkoxy, amide, halogen, hydroxyl, carboxyl, C1-6alkylcarbonyl and formyl. Particularly preferred R6 is a divalent methyl (methylene).

In some embodiments, R 7 comprises a free radical reactive group such as an acrylate, a styryl, vinyl, vinyl ether, itaconate group, a C 1-6 alkylacrylate, acrylamide, C 1-6 alkylacrylamide, N-vinylactam, N-vinylamide , C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthyl or C 2-6 alkenylphenylC 1-4 alkyl or a cationic reactive group such as vinyl ether or epoxide groups. Particularly preferred R7 is methacrylate.

In some embodiments, R8 is a divalent C1-6alkyl, C1-6 alkyloxy, C1-6alkyloxyC1-6alkyl, phenylene, naphthalene, Cl-12Cycloalkyl, C1-6 alkoxycarbonyl, amide, carboxy, C1-6alkylcarbonyl, carbonyl, C1-6alkoxy Substituted C1-6 alkyl, substituted C1-6 alkyloxy, substituted C1-6 alkyloxyC1-6 alkyl, substituted phenylene, substituted naphthalene, substituted C1-6 cycloalkyl, where substituents are selected from one or more members of the group consisting of C1-6aIoxycarbonyl, C1 -6alkyl, C1-6alkoxy, amide, halogen, hydroxyl, carboxyl, C1-6alkylcarbonyl and formyl. Particularly preferred R 8 is C 1-6 alkyloxyC 1-6 alkyl.

Examples of hydroxyl-functionalized silicone-containing monomer of Formula I include 2-propenoic acid, 2-methyl-2-hydroxy-3- [3- [1,3,3,3-tetramethyl-1 - [(trimethylsilyl) oxide ester] ] disiloxanyl] propoxy] propyl (which may also be called (3-methacryloxy-2-idroxypropyloxy) propylbis (trimethylsilyl) methylsilane) -2. The compound (3-methacryloxy-2-hydroxypropyloxy) propylbis (trimethylsiloxy) methylsilane may be formed of an epoxide, which produces an 80:20 mixture of the compound shown above and (2-methacryloxy-3-hydroxypropyloxy) propylbis ( trimethylsiloxy) methylsilane. In some embodiments of the present invention it is preferred to have some amount of the primary hydroxyl present, preferably greater than about 10 wt% and more preferably at least about 20 wt%.

Other hydroxyl-functionalized silicone-containing monomers include (3-methacryloxy-2-hydroxypropyloxy) propyltris (trimethylsilyl) silane 3-bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane 4-3-methacryloxy-2- (2-hydroxyethyl) propylisopropyl) (trimethyl (3-methacryloxy-2-hydroxypropyl) - alpha., omega., - bis-3-aminopropyl-polydimethylsiloxane.

Glycidyl methacrylate reaction products with amino functional polydimethylsiloxanes can also be used as a monomer containing hydroxyl functionalized silicone. Still additional structures which may be suitable hydroxyl-functionalized silicone-containing monomers include those similar to compounds having the following structure: where n = 1-50 and R independently comprises H or a polymerizable unsaturated group with at least one R comprising a polymerizable group, and at least one R 1 and preferably 3-8 R 1 comprising H. Such components may be removed from the hydroxyl-functional monomer by known methods such as liquid phase chromatography, distillation, recrystallization or extraction or its formation can be prevented by careful selection of reaction conditions and reagent reasons.

Suitable multifunctional hydroxyl-functionalized silicone-containing monomers are commercially available from Gelest, Inc., Morrisville, Pa. Suitable multifunctional hydroxyl-functionalized silicone-containing monomers are commercially available from Gelest, Inc., Morrisvile, Pa. Or may be made using standard procedures. known.

Although hydroxyl-functionalized silicone-containing monomers have been found to be particularly suitable for providing compatible polymers for biomedical devices, and particularly ophthalmic devices, any functionalized silicone-containing monomer which when polymerized and / or formed into a final article is compatible with The selected hydrophilic components can be used. Suitable monomers containing functionalized silicone may be selected using the following monomer compatibility test. In this test, one gram each of terminated mono-3-methacryloxypropyl, monobutyl terminated polydimethylsiloxane (mPDMS PM 900-1000) and a monomer to be tested are mixed together into one gram of 3,7-dimethyl-3 octanol at about 20 degrees C. A mixture of 12 parts by weight PVP K-90 and 60 parts by weight DMA is added dropwise to the hydrophobic component solution with stirring until the solution remains cloudy after three minutes. agitation. The mass of the added PVP and DMA mixture is determined in grams and recorded as the monomer compatibility index. Any hydroxyl functionalized silicone containing monomer having a compatibility index of more than 0.2 grams, more preferably greater than about 0.7 grams and more preferably greater than 1.5 grams will be suitable for use. in the present invention.

An "effective amount" or "compatibilizing effective amount" of the hydroxyl-functionalized silicone-containing monomers of the invention is the amount necessary to make compatible or dissolve the high molecular weight hydrophilic polymer and the other components of the hydrophilic formulation. polymer. Thus, the amount of hydroxyl-functionalized silicone-containing monomer will depend in part on the amount of hydrophilic polymer that is used, with more hydroxyl-functionalized silicone-containing monomer being required to match higher concentrations of hydrophilic polymer. Effective amounts of hydroxyl-functionalized silicone-containing monomer in the polymer formulation include about 5% (weight percent based on percent weight of reactive components) to about 90%, preferably about 10%. about 80%, more preferably about 20% to about 50%.

In addition to the high molecular weight hydrophilic polymers and hydroxyl functionalized silicone-containing monomers of the invention other hydrophilic and hydrophobic monomers, crosslinkers, additives, diluents, polymerization initiators may be used to prepare the biomedical devices of the invention. In addition to high molecular weight hydrophilic polymer and hydroxyl functionalized silicone-containing monomer, hydrogel formulations may include additional silicone-containing monomers, hydrophilic monomers and crosslinkers to provide the biomedical devices of the invention.

Additional Silicone Containing Monomers

For additional silicone-containing monomers, useful amide analogs of TRIS may include 3-methacryloxypropyltris (trimethylsilyl) silane (TRIS) 1 monomethacryloxypropyl-terminated polydimethylsiloxanes, polydimethylsiloxanes, 3-methacryloxypropylbis (trimethylsilyl) methyl criloxypropylpentamethyldisiloxane and combinations thereof are particularly useful as additional silicone containing monomers of the invention. Additional silicone-containing monomers may be present in amounts of from about 0 to about 75% by weight, more preferably from about 5 to about 60, and more preferably from about 10 to 40% by weight.

Hydrophilic Monomers

Additionally, reaction components of the present invention may also include any hydrophilic monomers used to prepare conventional hydrogels. For example, monomers containing acrylic groups (CH2.dbd.CRCOX, where R is hydrogen or C1-6alkyl and X is O or N) or vinyl groups (--C.dbd.CH2) may be used. Examples of additional hydrophilic monomers are Ν, Ν-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol monomethacrylate, 2-hydroxyethyl methacrylamide, polyethylene glycol monomethacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone, N-vinylamide , N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide and combinations thereof.

Apart from the additional hydrophilic monomers mentioned above, polyoxyethylene polyols having one or more of the terminal hydroxyl groups substituted with a functional group containing a polymerizable double bond may be used. Examples include polyethylene glycol, ethoxylated alkyl glycoside and ethoxylated bisphenol A, reacted with one or more molar equivalents of an end capping group such as isocyanatomethyl methacrylate, methacrylic anhydride, methacryloyl chloride, vinylbenzoyl chloride, and the like. a polyethylene polyol having one or more terminal polymerizable olefinic groups attached to the polyethylene polyol via bonding moieties such as carbamate, urea or ester groups.

Additional examples include hydrophilic vinyl carbonate or vinyl carbamate monomers, hydrophilic oxazolone monomers and polydextran. Additional hydrophilic monometers may include N, N-dimethylcrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), glycerol methacrylate, 2-hydroxyethyl methacrylamide, N-vinylpyrrolidone (NVP) 1 polyethylene glycol monomethacrylate, methacrylic acid acrylic acid and combinations thereof. Additional hydrophilic monomers may be present in amounts of from about 0 to about 70% by weight, more preferably from about 5 to about 60, more preferably from about 10 to about 50% by weight.

Crosslinkers

Suitable crosslinkers are composed of two or more polymerizable functional groups. The crosslinker may be hydrophilic or hydrophobic and in some embodiments of the present invention mixtures of hydrophilic and hydrophobic crosslinkers have been found to provide improved optical clarity silicone hydrogels (reduced cloudiness compared to CSI Thin Lens). Examples of suitable hydrophilic crosslinkers include compounds having two or more polymerizable functional groups, as well as hydrophilic functional groups such as polyether, amide or hydroxyl groups. Specific examples include TEGDMA (tetraethylene glycol dimethacrylate), TrEGDMA (triethylene glycol dimethacrylate), ethylene glycol dimethacrylate (EGDMA), ethylenediamine dimethylacrylamide, dimethacrylate glycerol and combinations thereof. Examples of suitable hydrophobic crosslinkers include multifunctional hydroxyl functionalized silicone containing monomers, multifunctional polyether polydimethylsiloxane block copolymers, combinations thereof and the like. Specific hydrophobic crosslinkers include acryloxypropyl (n = 10 or 20) terminated polydimethylsiloxane (acPDMS), hydroxyacrylated functional siloxane polymer, methacryloxypropyl terminated PDMS, butanediol dimethacrylate, divinyl benzene, 1,3-bis (3- methacryloxypropyl) tetracis (trimethylsiloxy) disiloxane and mixtures thereof. Preferred crosslinkers include TEGDMA, EGDMA, acPDMS and combinations thereof.

The amount of hydrophilic crosslinker used is generally about 0 to about 2 wt% and preferably from about 0.5 to about 2 wt% and the amount of hydrophobic crosslinker is about 0 to about 5% by weight, which may alternatively be referred to in mol% of about 0.01 to about 0.2 mmol / gm of reactive components, preferably about 0.02 to about 0.1 and with more preferably 0.03 to about 0.6 mmol / gm.

Increased crosslinker level in the final polymer has been found to reduce the amount of cloudiness. However, as crosslinking concentration increases above about 0.15 mmol / gm, the modulus of reactive components may increase above generally desired levels (greater than about 620.53 kPa (90 psi)). Then, in some embodiments of the present invention, the crosslinker composition and amount are selected to provide a crosslinker concentration in the reaction mixture between about 0.01 and about 0.1 mmol / gm of crosslinker.

Additional components or additives, which are generally known in the art, may also be included. Additives include, but are not limited to, ultraviolet absorption compounds and monomer, reactive dyes, antimicrobial compounds, pigments, photochromes, release agents, combinations thereof and the like.

Additional components include other oxygen permeable components such as carbon-carbon triple bond-containing monomers and fluorine-containing monomers which are known in the art and include fluorine-containing (meth) acrylates, and more specifically include, for example, C2 esters. -C12 alkyl of fluorine-containing (meth) acrylic acid such as 2,2,2-trifluoroethyl (meth) acrylate, 2,2,2,2 ', 2', 2'-hexafluoropropyl (meth) acrylate, 2,2,3,3,4,4,4-heptafluorbutyl (meth) acrylate, 2,2,3,3,4,4,5,5,6,6,7,7, (meth) acrylate, 8-8,8-pentadecafluoroctyl, (meth) acrylate 2,2,3,3,4,4,5, 5,6,6,7,7,8,8,9,9, -hexadecafluornonyl and the like. Thinners

Reaction components (hydroxyl-functionalized silicone-containing monomer, hydrophilic polymer, cross-linker (s) and other components) are generally mixed and reacted in the absence of water and optionally in the presence of at least one diluent to form a solvent. reaction mixture. The type and amount of diluent used also affects the properties of the resulting polymers and article. Cloudiness and wetting capacity of the final article may be improved by selective and relatively hydrophobic diluents and / or by decreasing the concentration of diluent used. As discussed above, increased hydrophobicity of the diluent may also allow poorly compatible components (as measured by the compatibility test) to be processed to form compatible polymer and article. However, as the diluent becomes more hydrophobic, processing steps required to replace the diluent with water will require the use of solvents other than water. This may undesirably increase the complexity and costs of the manufacturing process. Therefore, it is important to select a diluent that provides the desired compatibility with the components with the required processing convenience level. Diluents useful in preparing the devices of the present invention include ethers, esters, alkanes, alkyl halides, silanes, amides, alcohols and combinations thereof. Amides and alcohols are preferred diluents, and secondary and tertiary alcohols are more preferred alcohol diluents. Examples of ethers useful as diluents for the present invention include tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n- butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycols, polypropylene glycols and mixtures thereof. Examples of esters useful for the present invention include ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate. Examples of alkyl halides useful as diluents for the present invention include methylene chloride. Examples of silanes useful as diluents for the present invention include octamethylcyclotetrasiloxane.

Examples of alcohols useful as diluents for the present invention include those having formula 7, wherein R, R 'and R' are independently selected from H1 a linear, branched or cyclic monovalent alkyl having 1 to 10 carbons which optionally substituted with one or more groups including halogens, ethers, esters, aryls, amines, amides, alkenes, alkenes, carboxylic acids, alcohols, aldehydes, ketones or the like, or any two or all three of R, R 'and R "may bond to form one or more cyclic structures, such as alkyl having 1 to 10 carbons which may be substituted as described above, provided that no more than one of R, R 'and R" is H.

It is preferred that R, R 'and R "are independently selected from H or unsubstituted linear, branched or cyclic alkyl groups having 1 to 7 carbons. It is more preferred that R, R' and R" are independently selected. of unsubstituted linear, branched or cyclic alkyl groups having 1 to 7 carbons. In certain embodiments, the preferred diluent has 4 or more, more preferably 5 or more carbons in total, because higher molecular weight diluents have lower volatility and lower flammability. When one of R, R 'and R "is H, the structure forms a secondary alcohol. When none of R, R' and R" is H, the structure forms a tertiary alcohol. Tertiary alcohols are more preferred than secondary alcohols. The diluents are preferably inert and easily displaceable by water when the total number of carbons is five or less. Examples of useful secondary alcohols include 2-butanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2- heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol and the like.

Examples of useful tertiary alcohols include tert-butanol, tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2 -hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2,2-dimethyl-2-nonanol , 2-methyl-2-decane, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4 -octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol , 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene 4,4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol, 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl -3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol and the like.

A single alcohol or mixtures of two or more of the alcohols listed above or two or more alcohols according to the above structure may be used as the diluent to make the polymer of the present invention.

In certain embodiments, preferred alcohol diluents are secondary and tertiary alcohols having at least 4 carbons. In particular, some alcohol diluents may include t-butanol, tert-amyl alcohol, 2-butanol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 3- ethyl-3-pentanol, 3,7-dimethyl-3-octanol.

Diluents may also include: hexanol, heptanol, octanol, nanol, decanol, tert-butyl alcohol, 3-methyl-3-pentanol, isopropanol, t-amyl alcohol, ethyl lactate, methyl lactate, i-propyl lactate 3,7-dimethyl-3-octanol, dimethyl formamide, dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone and mixtures thereof.

In some embodiments of the present invention, the diluent is water soluble under processing conditions and readily removed from the lens with water in a short period of time. Suitable water soluble diluents include 1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, tripropylene glycol methyl ether, isopropanol, 1-methyl-2-pyrrolidone, N, N-dimethylpropionamide, Ethyl lactate, dipropylene glycol methyl ether, mixtures thereof and the like. The use of a water soluble diluent allows the post molding process to be conducted using water only or aqueous solutions comprising water as a substantial component.

In some embodiments, the amount of diluent may generally be less than about 50% by weight of the reaction mixture and preferably less than about 40% and more preferably between about 10 and about 30%. In some embodiments, diluent may also include additional components such as release agents and may include water soluble and lens release aid. Polymerization initiators may include, for example, compounds such as lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile and the like which generate moderately high free radicals and photoinitiating systems such as alpha hydroxy ketones alkoxyoxybenzoines, acetophenones, acyl phosphine oxides and tertiary amine plus a diketone, mixtures thereof and the like. Illustrative examples of photoinitiators are 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis (2,6-dimethoxybenzoyl) -2,4,4-trimethyl-oxide. pentyl phosphine (DMBAPO), bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide (Irrature 819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and 2,4,6-trimethylbenzoyl diphenylphosphine oxide benzoin methyl ester and a combination of camphorquinone and ethyl 4- (N, N-dimethylamino) benzoate. Commercially available visible light primer systems include Irgacure 819, Irgacure 1700, Irgacure 1800, Irgacure 819, Irgacure 1850 (all from Ciba Specialty Chemicals) and Lucirin TPO primer (available from BASF). Commercially available UV photoinitiators include Darocur 1173 and Darocur 2959 (Ciba Specialty Chemicals). The initiator is used in the reaction mixture in amounts effective to initiate photopolymerization of the reaction mixture, for example from about 0.1 to about 2 parts by weight per 100 parts of reactive monomer. Polymerization of the reaction mixture may be initiated using the appropriate choice of heating or visible or ultraviolet light or other means depending on the polymerization initiator used. Alternatively, initiation may be conducted without a photoinitiator using, for example, electron beam. However, when a photoinitiator is used, some embodiments may include a combination of 1-hydroxycyclohexyl phenyl ketone and bis (2,6-dimethoxybenzoyl) -2,4,4-trimethylpentyl phosphine oxide (DM-BAPO), and The polymerization initiation method may include visible light. Other embodiments may include: bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide (Irgacure 819. RTM.).

In some embodiments, the present invention may further include ophthalmic lenses of the formulas: 1% by weight of HFSCM HMWHP SCM HM components 5-90, 1-15, 3-15 or 5-1200 10-80 1-15, 3-15 or 5-12 00 20-50 1-15, 3-15 or 5-12 00 5-90 1-15, 3-15 or 5-12 0-80, 5-60 or 10-0-70 5-60 or 10-40 50 10-80 1-15, 3-15 or 5-12 0-80, 5-60 or 10-0-70, 5-60 or 10-40 50 20-50 1- 15, 3-15 or 5-12 0-80, 5-60 or 10-0-70, 5-60 or 10-40 50 HFSCM is hydroxyl functionalized silicone-containing monomer HM-WHP is SCM high molecular weight hydrophilic polymer is monomer containing silicone and HM is hydrophilic monomer.

The above weight percentages may be based on all reactive components. Thus, in some embodiments, the present invention may include one or more of: silicone hydrogels, biomedical devices, ophthalmic devices, and contact lenses, each of one or more of the compositions listed in the table, which describes ninety bands. possible compositional Each of the ranges considered may be prefixed with "about", so the range combinations shown as long as the components listed, and any additional components add up to 100% by weight.

A range of the combined silicone-containing monomers (hydroxyl-functionalized silicone-containing monomers and additional silicone-containing monomers) may be from about 5 to 99 percent by weight, more preferably about 15 to 90 percent. by weight, and in some embodiments about 25 to about 80 weight percent of the reaction components. A hydroxyl functionalized silicone-containing monomer range may be from about 5 to about 90 weight percent, preferably from about 10 to about 80 weight, and more preferably from about 20 to about 50 weight percent. In some embodiments, a hydrophilic monomer range may be from about 0 to about 70 weight percent, more preferably about 5 to about 60 weight percent, and more preferably about 10 to about 70 weight percent. 50 percent by weight of reactive components. In other embodiments, a high molecular weight hydrophilic polymer range may be about 1 to about 15 weight percent, or about 3 to about 15 weight percent, or about 5 to about 12 weight percent. percent by weight. All weight percentages above are based on the total of all reactive components. In some embodiments, a diluent range is from about 0 to about 70 weight percent or about 0 to about 50 weight percent and / or about 0 to about 40 weight percent. and, in some embodiments, from about 10 to about 30 weight percent, based on the weight of all components in the reaction mixture. The amount of diluent required varies depending on the nature and relative quantities of the reactive components.

In some embodiments, the reactive components comprise 2-propenoic acid, 2-methyl-2-hydroxy-3- [3- [1,3,3,3-tetramethyl-1 - [(trimethylsilyl) oxide] disiloxanyl] ester propoxy] propyl "SiGMA" (about 28% by weight of reaction components); monomethacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane of PM 800-1000, "mPDMS" (about 31 wt%); Î ±, Î ± -dimethylacrylamide, "DMA" (about 24 wt%); 2-hydroxyethyl methacrylate, "HEMA" (about 6 wt%); tetraethylene glycol dimethylacrylate; "TEGDMA" (about 1.5 wt%), "PVP K-90" polyvinylpyrrolidone (about 7 wt%); with equilibrium comprising small amounts of additives and photoinitiators. Polymerization may also be conducted in the presence of about 23% (wt.% Of the combined monomers and diluent mixture) of 3,7-dimethyl-3-octanol diluent.

In some embodiments, polymerizations for the above formulations may be conducted in the presence of tert-amyl alcohol as a diluent comprising about 29 weight percent of the uncured reaction mixture.

Processing

Modalities may include ophthalmic lenses of the present invention which are prepared by mixing the high molecular weight hydrophilic polymer, the hydroxyl functionalized silicone-containing monomer, plus one or more of the following: the additional silicone-containing monomers, the monomers hydrophilic compounds, additives ("Reactive Components") and diluents (collectively the "Reaction Mix") with a polymerization initiator and curing the Reaction Mix under appropriate conditions to form a product which can subsequently be formed into a preformed format. - Finished by turning, cutting and the like. Alternatively, the reaction mixture may be cast into a mold and subsequently cured into a suitable article.

Several processes are known for reaction mixture processing in the production of contact lenses, including rotary casting and static casting. In some embodiments, the method for producing polymer contact lenses of the present invention is by molding the silicone hydrogels. During molding, the Reaction Mix is put into a mold having the shape of the final desired silicone hydrogel, i.e., water-swollen polymer, and the reaction mixture is subjected to conditions with which the monomers polymerize, to then produce a polymer / diluent mixture in the shape of the final desired product. Then, this polymer / diluent mixture is treated with a solution to remove the diluent and eventually replace it with water, producing a silicone hydrogel having a final size and shape that is quite similar to the size and shape of the polymer article. / original molded thinner. Cure

Another aspect of some embodiments of the present invention includes curing silicone hydrogel formulations in a manner that provides increased wetting capacity. In accordance with the present invention, it has been found that the gel time for a silicone hydrogel may be related to curing conditions to provide a wetting ophthalmic device, and specifically a contact lens. As used herein, gel time is the time at which a crosslinked polymer network is formed, resulting in the viscosity of the curing reaction mixture approaching infinity and the reaction mixture becoming non-fluid. The gel point happens at a specific degree of conversion, regardless of reaction conditions, and can then be used as an indicator of reaction rate. It has been found that for a given reaction mixture the gel time can be used to determine curing conditions that offer desirable wetting capacity. Thus, in some embodiments of the present invention, the reaction mixture may be cured at or above a gel time providing improved wetting capacity, and in some embodiments of sufficient wetting capacity for the resulting device to be used without a coating. hydrophilic coating or surface treatment ("minimum gel time"). In some embodiments, improved wetting capacity may be a decrease in advanced dynamic contact angle of at least 10% compared to formulation without any high molecular weight polymer. In some embodiments, therefore, longer gel times are preferred since they provide improved wetting capacity and increased processing flexibility.

Gel times may vary for different silicone hydrogel formulations. Curing conditions may also affect gel time. For example, in some embodiments, crosslinking concentration will impact gel time, where increasing crosslinking concentrations decreases gel time. Increased radiation intensity (for photopolymerization) or temperature (for thermal polymerization), initiation efficiency (either by selecting a more efficient initiator or irradiation source, or an initiator that absorbs more strongly in the range). selected irradiation) will also decrease the gel time. Temperature and type and concentration of diluent may also affect gel time in ways known to those skilled in the art.

In some embodiments, a minimum gel time may be determined by selecting a given formulation, varying one of the above factors, and measuring gel time and contact angles. The minimum gel time may then be the point above which the resulting lens is generally humectant. Below the minimum gel time, the lens may be non-wetting. In the context of the present disclosure, for a "generally wetting" contact lens is a lens showing an advanced dynamic contact angle of less than about 80 degrees, and in some embodiments less than 70 degrees and still in other modalities less than about 60 degrees. Then those skilled in the art will understand that the minimum gel point as defined herein may be a range, taking into account experimental statistical variability. In certain embodiments, use of minimum visible light radiation gel times of at least about 30 seconds has been found to be advantageous.

In some embodiments, a mold containing the Reaction Mixture is exposed to ionizing or actinic radiation, for example electron beams, X-rays, UV or visible light, i.e. electromagnetic radiation or particle radiation having a length wavelengths from about 150 to about 800 nm. In some embodiments, the radiation source is UV or visible light having a wavelength of about 250 to about 700 nm. Suitable sources of radiation may include UV lamps, fluorescent lamps, incandescent lamps, mercury vapor lamps, and sunlight. In embodiments, where the UV-absorbing compound is included in the composition (e.g., as a UV block) curing is conducted by means other than UV irradiation (such as through visible light or heat). In some preferred embodiments, the radiation source may be selected from UVA (about 315-400 nm), UVB (about 280-315) or visible light (about 400-450 nm) ) at low intensity.

In other embodiments, the reaction mixture includes a UV absorbing compound, is cured using visible light and low intensity. As used herein, the term "low intensity" means those between about 0.1 mW / cm2 to about 6 mW / cm2 and preferably between about 0.2 mW / cm2 and 3 mW / cm2. The curing time may then be relatively long, generally more than about 1 minute and preferably between about 1 and about 60 minutes and most preferably between about 1 and about 30 minutes. In some embodiments, relatively slow, relatively slow cure may provide compatible ophthalmic devices that show lasting resistance to protein deposition in vivo.

In some embodiments, the temperature at which the reaction mixture is cured may be raised above ambient, where the cloudiness of the resulting polymer decreases. Effective temperatures for reducing cloudiness include temperatures at which cloudiness to the resulting lens is decreased by at least about 20% as compared to a lens of the same composition made at 25 ° C. Thus, in some embodiments, suitable curing temperatures may include temperatures greater than about 25 degrees C. Specifically, embodiments may include ranges between about 25 degrees C and 70 degrees C and between about 40 degrees C and 70 degrees. C. Precise adjustment of curing conditions (temperature, intensity and time) may depend on the components of the lens material selected and, with reference to the present teaching, is within the skill of the art to determine. Curing may be conducted in one or a plurality of curing zones, and should preferably be sufficient to form a polymer network from the reaction mixture. Typically, the resulting polymer network may be swollen with the diluent and shaped like the mold cavity.

Examples:

Lenses can be made according to the above descriptions and with 24 parts Ν, Ν-dimethylacrylamide and 0.48 ppm CGI 1850 using concave mold parts combined with convex molds. After photocure, the mold parts are removed, and the lenses on the concave mold part were placed in stirring aqueous solutions as shown in Table 1. Each aqueous solution included an alcohol as indicated in the column "Agent" in Table 1. The time until the lens detached and completely detached from the molds was measured and is additionally shown in Table 1.

As indicated in Table 1, exposure to aqueous solutions including alcohols additionally had the effect of leaching D3O from the lens.

The lenses were shaken in their respective aqueous solutions for a total time as indicated in Table 1, then removed and extracted with isopropanol to remove residual D30 diluent. Isopropanol extract was analyzed for D3O and the results are shown in Table 1 as a percentage of the level found in unbleached control lenses. Table 1

<table> table see original document page 34 </column> </row> <table>

Claims (80)

A method for releasing an ophthalmic lens comprising silicone from a part of the mold, the method comprising: exposing said ophthalmic lens to a first aqueous solution comprising about 4% or more of 2-pentanol; and heating said first aqueous solution to which the ophthalmic lens is exposed. A method according to claim 1, further comprising the steps of: removing unreacted components and diluents from an ophthalmic lens by exposing the lens to the first aqueous solution; and rinsing said ophthalmic lens by contacting a second aqueous solution until said lens comprises a level of unreacted components and diluents that is below a predetermined threshold. A method according to claim 2, wherein the lens is exposed to the first aqueous solution for approximately 20 minutes or more. The method of claim 2, wherein said first liquid, said second liquid or both comprises a buffered aqueous solution. A method according to claim 4, wherein said first liquid, said second liquid or both comprise sodium chloride, boric acid, sodium borate, sodium dihydrogen phosphate, sodium citrate, sodium acetate. , baking soda or any combination thereof. The method of claim 2, wherein the predetermined threshold comprises a detection threshold for unreacted components and diluents. The method of claim 2, wherein said ophthalmic lens comprises a contact lens comprising from 0 to about 90 percent water. The method of claim 2, wherein said ophthalmic lens further comprises a diluent and said method further comprising removing said diluent from said ophthalmic lens. The method of claim 8, wherein said ophthalmic lens has a functional size and swells during said diluent removal. The method of claim 2, wherein said ophthalmic lens is colored. A method according to claim 2, wherein said ophthalmic lens comprises a staining pattern. The method of claim 2, wherein said ophthalmic lens is formed of a reaction mixture comprising high molecular weight hydrophilic polymer and an effective amount of a hydroxyl functionalized silicone containing monomer. The biomedical device of claim 2, wherein the effective amount of said hydroxyl functionalized silicone-containing monomer is from about 5% to about 90%. The method of claim 1, wherein the ophthalmic lens is formed of a reaction mixture comprising from about 1% to about 15% of high molecular weight hydrophilic polymer. The method of claim 1, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl 2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole , poly-N, N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2-ethyl oxazoline, heparin polysaccharides, polysaccharides, mixtures and their copolymers. The method of claim 2, wherein the ophthalmic lens rinse step comprises exposing the ophthalmic lens three times to at least 35 ml of deionized water. A method according to claim 2, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: N, N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol methacrylate, -hydroxyethyl methacrylamide, polyethylene glycol monomethacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, hydrophilic vinyl carbonate monomers, vinyl carbamate monomers, hydrophilic oxazolone monomers and polydextran. The method of claim 2, wherein the first aqueous solution is heated to about 90 ° C or more. The method of claim 2, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises immersing the lens in the first aqueous solution. The method of claim 2, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises flow of the first aqueous solution onto the lens. A method for releasing an ophthalmic lens comprising silicone from a part of the mold, the method comprising: exposing said ophthalmic lens to a first aqueous solution comprising about 4% or more of 2-pentanol and 0.5% or more than C12E10 and 0.05% or more of SCAW; and heating said first aqueous solution to which the ophthalmic lens is exposed. The method of claim 21, further comprising the steps of: removing unreacted components and diluents from an ophthalmic lens by exposing the lens to the first aqueous solution; and rinsing said ophthalmic lens through contact with a second aqueous solution until said lens comprises a level of unreacted components and diluents that is below a predetermined threshold. The method of claim 22, wherein the lens is exposed to the first aqueous solution for approximately 20 minutes or more. The method of claim 22, wherein said first liquid, said second liquid or both comprises a buffered aqueous solution. The method of claim 24, wherein said first liquid, said second liquid or both comprises sodium chloride, boric acid, sodium borate, sodium dihydrogen phosphate, sodium citrate, sodium acetate. , baking soda or any combination thereof. The method of claim 22, wherein the predetermined threshold comprises a detection threshold of unreacted components and diluents. The method of claim 22, wherein said ophthalmic lens comprises a contact lens comprising from 0 to about 90 percent water. The method of claim 22, wherein said ophthalmic lens further comprises a diluent and said method further comprising removing said diluent from said ophthalmic lens. The method of claim 28, wherein said ophthalmic lens has a functional size and swells during said diluent removal. The method of claim 22, wherein said ophthalmic lens is colored. The method of claim 22, wherein said ophthalmic lens comprises a staining pattern. The method of claim 22, wherein said ophthalmic lens is formed of a reaction mixture comprising high molecular weight hydrophilic polymer and an effective amount of a hydroxyl-functionalized silicone-containing monomer. The biomedical device of claim 22, wherein the effective amount of said hydroxyl functionalized silicone-containing monomer is about 5% to about 90%. The method of claim 22, wherein the ophthalmic lens is formed of a reaction mixture comprising about 1% to about 15% high molecular weight hydrophilic polymer. The method of claim 22, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl 2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole , poly-N, N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2-ethyl oxazoline, heparin polysaccharides, polysaccharides, mixtures and their copolymers. The method of claim 22, wherein the ophthalmic lens rinse step comprises exposing the ophthalmic lens three times to at least 35 ml of deionized water. The method of claim 22, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: N, N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol methacrylate, -hydroxyethyl methacrylamide, polyethylene glycol monomethacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, hydrophilic vinyl carbonate monomers, vinyl carbamate monomers, hydrophilic oxazolone monomers and polydextran. The method of claim 22, wherein the first aqueous solution is heated to about 90 ° C or more. The method of claim 22, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises dipping the lens into the first aqueous solution. The method of claim 22, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises flow of the first aqueous solution onto the lens. 41. A method for releasing an ophthalmic lens comprising silicone from a part of the mold, the method comprising: exposing said ophthalmic lens to a first aqueous solution comprising about 2% or more of a first releasing agent comprising n-hexanol. and 1% or more of C12E10 and 1% or more of SCAW; and heating said first aqueous solution to which the ophthalmic lens is exposed. A method according to claim 41, further comprising the steps of: removing unreacted components and diluents from an ophthalmic lens by exposing the lens to the first aqueous solution; and rinsing said ophthalmic lens by contacting a second aqueous solution until said lens comprises a level of unreacted components and diluents that is below a predetermined threshold. A method according to claim 42, wherein the lens is exposed to the first aqueous solution for approximately 20 minutes or more. The method of claim 42, wherein said first liquid, said second liquid or both comprises a buffered aqueous solution. A method according to claim 44, wherein said first liquid, said second liquid or both comprises sodium chloride, boric acid, sodium borate, sodium dihydrogen phosphate, sodium citrate, sodium acetate. , baking soda or any combination thereof. The method of claim 42, wherein the predetermined threshold comprises a detection threshold of unreacted components and diluents. A method according to claim 42, wherein said ophthalmic lens comprises a contact lens comprising from 0 to about 90 percent water. The method of claim 42, wherein said ophthalmic lens further comprises a diluent and said method further comprising removing said diluent from said ophthalmic lens. The method of claim 48, wherein said ophthalmic lens has a functional size and swells during said diluent removal. The method of claim 42, wherein said ophthalmic lens is colored. A method according to claim 42, wherein said ophthalmic lens comprises a staining pattern. The method of claim 42, wherein said ophthalmic lens is formed of a reaction mixture comprising high molecular weight hydrophilic polymer and an effective amount of a hydroxyl functionalized silicone-containing monomer. The biomedical device of claim 42, wherein the effective amount of said hydroxyl functionalized silicone-containing monomer is about 5% to about 90%. The method of claim 42, wherein the ophthalmic lens is formed of a reaction mixture comprising from about 1% to about 15% high molecular weight hydrophilic polymer. The method of claim 42, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl 2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole , poly-N, N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2-ethyl oxazoline, heparin polysaccharides, polysaccharides, mixtures and their copolymers. The method of claim 42, wherein the ophthalmic lens rinse step comprises exposing the ophthalmic lens three times to at least 35 ml of deionized water. A method according to claim 42, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: N, N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol methacrylate, -hydroxyethyl methacrylamide, polyethylene glycol monomethacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, hydrophilic vinyl carbonate monomers, vinyl carbamate monomers, hydrophilic oxazolone monomers and polydextran. A method according to claim 42, wherein the first aqueous solution is heated to about 90 ° C or more. The method of claim 42, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises dipping the lens into the first aqueous solution. The method of claim 42, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises flow of the first aqueous solution onto the lens. 61. A method for releasing an ophthalmic lens comprising silicone from a part of the mold, the method comprising: exposing said ophthalmic lens to a first aqueous solution comprising about 2% or more of a first releasing agent comprising n-hexanol. and 1% or more of C12E10 and 1% or more of SCAW; and heating said first aqueous solution to which the ophthalmic lens is exposed. A method according to claim 61, further comprising the steps of: removing unreacted components and diluents from an ophthalmic lens by exposing the lens to the first aqueous solution; and rinsing said ophthalmic lens through contact with a second aqueous solution until said lens comprises a level of unreacted components and diluents that is below a predetermined threshold. A method according to claim 61, wherein the lens is exposed to the first aqueous solution for approximately 20 minutes or more. A method according to claim 61, wherein said first liquid, said second liquid or both comprises a buffered aqueous solution. A method according to claim 64, wherein said first liquid, said second liquid or both comprises sodium chloride, boric acid, sodium borate, sodium dihydrogen phosphate, sodium citrate, sodium acetate. , baking soda or any combination thereof. The method of claim 62, wherein the predetermined threshold comprises a detection threshold for unreacted components and diluents. A method according to claim 62, wherein said ophthalmic lens comprises a contact lens comprising from 0 to about 90 percent water. A method according to claim 62, wherein said ophthalmic lens further comprises a diluent and said method further comprising removing said diluent from said ophthalmic lens. The method of claim 68, wherein said ophthalmic lens has a functional size and swells during said diluent removal. 70. The method of claim 62, wherein said ophthalmic lens is colored. 71. The method of claim 62, wherein said ophthalmic lens comprises a staining pattern. The method of claim 62, wherein said ophthalmic lens is formed of a reaction mixture comprising high molecular weight hydrophilic polymer and an effective amount of a hydroxyl functionalized silicone containing monomer. The biomedical device of claim 62, wherein the effective amount of said hydroxyl functionalized silicone-containing monomer is about 5% to about 90%. The method of claim 62, wherein the ophthalmic lens is formed of a reaction mixture comprising from about 1% to about 15% high molecular weight hydrophilic polymer. 75. The method of claim 62, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl 2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone and poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole , poly-N, N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid, polyethylene oxide, poly-2-ethyl oxazoline, heparin polysaccharides, polysaccharides, mixtures and their copolymers. The method of claim 62, wherein the ophthalmic lens rinse step comprises exposing the ophthalmic lens three times to at least 35 ml of deionized water. A method according to claim 62, further comprising the step of forming the ophthalmic lens by curing a monomer comprising the group consisting of: N, N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol methacrylate, -hydroxyethyl methacrylamide, polyethylene glycol monomethacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, hydrophilic vinyl carbonate monomers, vinyl carbamate monomers, hydrophilic oxazolone monomers and polydextran. A method according to claim 62, wherein the first aqueous solution is heated to about 90 ° C or more. The method of claim 62, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises immersing the lens in the first aqueous solution. The method of claim 62, wherein the step of exposing said ophthalmic lens to a first aqueous solution comprises flow of the first aqueous solution onto the lens.