HK1199895B - Silicone hydrogels having improved curing speed and other properties - Google Patents

Description

Silicone hydrogels with improved cure speed and other properties

RELATED APPLICATIONS

The present application claims priority from U.S. provisional patent application 61/541,556 entitled silicon hydride bearing SPEED AND OTHER PROPERTIES filed 30.9.2011 AND U.S. patent application 13/604,680 filed 6.9.2012, filed 5.4, the contents of which are incorporated herein by reference.

Technical Field

The present invention relates to silicone polymer/silicone hydrogels and ophthalmic devices, such as contact lenses formed from silicone polymer/silicone hydrogels.

Background

Since the 50 s of the 20 th century, contact lenses have been commercialized to improve vision. The first contact lenses were made of hard materials. Although these lenses are still used today, they are not suitable for all patients due to their poor initial comfort and relatively low oxygen permeability. Subsequent developments in this area have resulted in soft contact lenses based on hydrogels, which are extremely popular today. Many users find soft lenses more comfortable and the increased comfort level may allow soft contact lens users to wear lenses for longer periods of time than users of hard contact lenses.

Hydrogels are hydrated cross-linked polymer systems containing water in an equilibrium state. Hydrogels are generally oxygen permeable and biocompatible, making them a preferred material for the preparation of biomedical devices, particularly contact or intraocular lenses.

Conventional hydrogels are made from a monomer mixture that contains primarily hydrophilic monomers such as 2-hydroxyethyl methacrylate ("HEMA") or N-vinyl pyrrolidone ("NVP"). The formation of conventional hydrogels is disclosed in U.S. patents 3,220,960, 4,495,313, 4,889,664, and 5,039,459. Blends of such mixtures are typically cured using thermal or photoactivated initiators. The time required to cure such blends is typically from minutes to over 24 hours. In commercial processes, it is preferred that the cure time be short. The resulting polymer swelled in water. The absorbed water softens the resulting hydrogel and allows some degree of oxygen permeability.

The present invention relates to the following findings: 2-hydroxyethyl acrylamide-containing silicone polymers/hydrogels having improved cure speed and other properties and ophthalmic devices, such as contact lenses, formed therefrom.

Disclosure of Invention

In one aspect, the invention relates to: a silicone polymer formed from reactive components comprising (i) at least one silicone component and (ii) 2-hydroxyethyl acrylamide; a silicone hydrogel containing such a silicone polymer; a biomedical device (e.g., a contact lens) comprising such a polymer; and a biomedical device formed from such a hydrogel.

Other features and advantages of the invention will be apparent from the description of the invention and from the claims.

Detailed Description

It is believed that one skilled in the art can, using the description herein, utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference.

Definition of

As used herein, a "biomedical device" is any article designed for use in or on mammalian tissue or fluid. Examples of such devices include, but are not limited to, catheters, implants, stents, and ophthalmic devices (e.g., intraocular lenses and contact lenses).

As used herein, an "ophthalmic device" is any device that is located in or on the eye or any part of the eye (including the cornea, eyelids, and ocular glands). These devices may provide optical correction, cosmetic, visual enhancement, therapeutic benefit (e.g., as a bandage), or delivery of an active component (e.g., a pharmaceutical or neutraceutical component), or a combination of any of the foregoing. Examples of ophthalmic devices include, but are not limited to, lenses and optical and ophthalmic inserts (including, but not limited to, punctal plugs, etc.).

As used herein, the term "lens" refers to an ophthalmic device that is located in or on the eye. The term lens includes, but is not limited to, soft contact lenses, hard contact lenses, intraocular lenses, and overlay lenses.

In one embodiment, the biomedical devices, ophthalmic devices, and lenses of the present invention comprise silicone polymers or silicone hydrogels. These silicone hydrogels typically contain a silicone component and/or hydrophobic and hydrophilic monomers that are covalently bonded to each other in the cured device.

As used herein, "reactive mixture" refers to a mixture of components (reactive and non-reactive) that are mixed together and subjected to polymerization conditions to form the silicone hydrogels of the present invention. The reactive mixture includes reactive components such as monomers, macromers, prepolymers, crosslinkers, and initiators, and additives such as wetting agents, mold release agents, dyes, light absorbing compounds (such as UV absorbers and photochromic compounds), any of which may be reactive or non-reactive but capable of being retained within the resulting biomedical device, as well as pharmaceutical and nutraceutical compounds. It is understood that a wide range of additives may be added based on the biomedical device produced and its intended use. The concentrations of the components of the reactive mixture are given as weight percent of all components in the reaction mixture except the diluent. When diluents are used, their concentrations are given in weight percent based on the amount of all components and diluents in the reaction mixture.

Silicone component

The silicone-containing component (or silicone component) is a component that contains at least one [ -Si-O-Si ] group in a monomer, macromer or prepolymer. In one embodiment, the Si and attached O are present in the silicone-containing component in an amount greater than 20 weight percent, such as greater than 30 weight percent, based on the total molecular weight of the silicone-containing component. Useful silicone-containing components contain polymerizable functional groups such as acrylate, methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinyl amide, and styryl functional groups. Examples of silicone-containing components useful in the present invention can be found in U.S. Pat. nos. 3,808,178; 4,120,570, respectively; 4,136,250; 4,153,641; 4,740,533, respectively; 5,034,461; 5,962,548, respectively; 5,998,498, respectively; and 5,070,215, and european patent 080539.

Suitable organosilicon-containing components include compounds of the formula I

Wherein:

R¹independently selected from a monovalent reactive group, a monovalent alkyl group, or a monovalent aryl group, any of which may further comprise a functional group selected from hydroxyl, amino, oxa, carboxyl, alkylcarboxyl, alkoxy, amide, carbamate, carbonate, halogen, or a combination thereof; and a monovalent siloxane chain comprising 1 to 50 Si-O repeating units (in some embodiments between 1 and 20 and between 1 and 10) that may further comprise a functional group selected from alkyl, hydroxyl, amino, oxa, carboxyl, alkylcarboxyl, alkoxy, amido, carbamate, halogen, or a combination thereof;

where b is 0 to 100 (in some embodiments 0 to 20 or 0-10), where it is understood that when b is not 0, b is a distribution having a mode equal to the specified value; and is

Wherein at least one R¹Contain monovalent reactive groups, and in some embodiments 1 to 3R¹Comprising a monovalent reactive group.

As used herein, a "monovalent reactive group" is a group that can undergo free radical and/or cationic polymerization. Non-limiting examples of free radical reactive groups include (meth) acrylates, styryl, vinyl ether, C_1-6Alkyl (meth) acrylates, (meth) acrylamides, C_1-6Alkyl (meth) acrylamides, N-vinyllactams, N-vinylamides, C_2-12Alkenyl radical, C_2-12Alkenylphenyl radical, C_2-12Alkenylnaphthyl, C_2-6Alkenylphenyl radical, C_1-6Alkyl, O-vinyl carbamate, and O-vinyl carbonate. Non-limiting examples of cationically reactive groups include vinyl ether or epoxy groups and mixtures thereof. In one embodiment, the free radical reactive group includes (meth) acrylates, acryloxys, (meth) acrylamides, and mixtures thereof. (meth) acrylic acid C_1-6Alkyl ester, C_1-6Alkyl (meth) acrylamides, N-vinyllactams, N-vinylamides, C_2-12Alkenyl radical, C_2-12Alkenylphenyl radical, C_2-12Alkenylnaphthyl, C_2-6Alkenyl phenyl C_1-6The alkyl groups may be substituted with hydroxyl groups, ether groups, or combinations thereof.

Suitable monovalent alkyl and aryl groups include unsubstituted monovalent C₁To C₁₆Alkyl radical, C₆-C₁₄Aryl groups such as methyl, ethyl, propyl, butyl, 2-hydroxypropyl, propoxypropyl, polyethyleneoxypropyl, combinations thereof, and the like.

In one embodiment, b is 0, 1R¹Is a monovalent reactive group and at least 3R¹Selected from monovalent alkyl groups having 1 to 16 carbon atoms (selected from monovalent alkyl groups having 1 to 6 carbon atoms in another embodiment), and 1R in another embodiment¹Is a monovalent reactive group, 2R¹Is trialkylsiloxy radical, the remainder R¹Is methyl, ethyl or phenyl, and in yet another embodiment, 1R¹Is a reactive group, 2R¹Is trialkylsiloxy radical, the remainder R¹Is methyl. Non-limiting examples of the silicone component of this embodiment include acrylic acid, -2-methyl-, 2-hydroxy-3- [3- [1,3,3, 3-tetramethyl-1- [ (trimethylsilyl) oxy]-1-disiloxanyl]Propoxy group]Propyl ester ("SiGMA"; structure in formula II),

2-hydroxy-3-methacryloxypropoxypropyl-tris (trimethylsiloxy) silane,

3-methacryloxypropyltris (trimethylsiloxy) silane ("TRIS"),

3-methacryloxypropyl bis (trimethylsiloxy) methylsilane and

3-methacryloxypropylpentamethyldisiloxane.

In another embodiment, b is2 to 20, 3 to 15, or in some embodiments 3 to 10; at least one terminal R¹Comprising monovalent reactive groups, the remainder of R¹Selected from monovalent alkyl groups having 1 to 16 carbon atoms, and in another embodiment, selected from monovalent alkyl groups having 1 to 6 carbon atoms. In another embodiment, b is 3 to 15, one terminal R¹Comprising a monovalent reactive group, the other terminal R¹Comprising a monovalent alkyl group having 1 to 6 carbon atoms and the remainder R¹Comprising a monovalent alkyl group having 1 to 3 carbon atoms. Non-limiting examples of the silicone component of this embodiment include (mono- (2-hydroxy-3-methacryloxypropyl) -propyl ether terminated polydimethylsiloxane (400-1000MW)) ("OH-mPDMS"; structure in formula III),

wherein R is₃Is C1-6 alkyl, and b is as defined above. An example of a suitable HO-mPDMS is

Additional examples of the silicone component of this embodiment include monomethacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxane (800-.

And is

In another embodiment, 1 terminal R¹Is C-containing which may be substituted on the amide N by C1-3 alkyl or hydroxyalkyl_1-6A monovalent reactive group of an alkyl (meth) acrylamide, b is 1 to 10, and the other end R is¹Selected from C1-4 alkyl, the remainder R¹Is methyl or ethyl. Such silicone containing components are disclosed in US 2011/237766.

In one embodiment, the silicone-containing component is a polymerizable ester, such as a (meth) acrylate.

In another embodiment, the silicone component includes polydimethylsiloxane dimethacrylate with pendant hydroxyl groups (such as compounds C2, C4 or R2 described in U.S. patent application 2004/0192872, or as examples XXV, XXVIII or XXXII described in U.S. patent 4,259,467), polymerizable polysiloxane with pendant hydrophilic groups (such as those disclosed in US 6867245). In some embodiments, the pendant hydrophilic groups are hydroxyalkyl or polyalkylene ether groups, or a combination thereof. The polymerizable polysiloxane may also contain fluorocarbon groups. One example is shown as structure B3.

In another embodiment, b is 5 to 400 or 10 to 300, both terminal R¹Each containing a monovalent reactive group and the remainder of R¹Independently selected from monovalent alkyl groups having 1 to 18 carbon atoms, which may have ether linkages between carbon atoms and may further comprise halogen.

In another embodiment, 1 to 4R¹Comprising a vinyl carbonate or vinyl carbamate of formula V:

wherein: y represents O-, S-or NH-; r represents hydrogen or methyl; and q is 0 or 1.

The silicone-containing vinyl carbonate or vinyl carbamate monomers include, in particular: 1, 3-bis [4- (vinyloxycarbonyloxy) but-1-yl ] tetramethyl-disiloxane; 3- (vinyloxycarbonylthio) propyl- [ tris (trimethylsiloxy) silane ]; 3- [ tris (trimethylsiloxy) silyl ] propylallylcarbamate; 3- [ tris (trimethylsiloxy) silyl ] propylvinylcarbamate; trimethylsilylethylethyl ethylene carbonate; trimethylsilylmethyl vinyl carbonate, and a compound of formula VI.

In the case where the modulus of the biomedical device is desired to be below about 200, there is only one R¹Should contain monovalent reactive groups and the remainder of R¹No more than two of the groups will comprise monovalent siloxane groups.

Another suitable silicone-containing macromer is a compound of formula VII (wherein x + y is a number in the range of 10 to 30) formed by the reaction of fluoroether, hydroxy-terminated polydimethylsiloxane, isophorone diisocyanate, and isocyanatoethyl methacrylate.

Other silicone components suitable for use in the present invention include those described in WO96/31792, such as macromers containing polysiloxane, polyalkylene ether, diisocyanate, polyfluorocarbon, polyfluoroether and polysaccharide groups. Another class of suitable silicone-containing components includes silicone-containing macromers prepared via GTP, such as those disclosed in U.S. Pat. nos. 5,314,960, 5,331,067, 5,244,981, 5,371,147, and 6,367,929. U.S. patents 5,321,108, 5,387,662, and 5,539,016 describe polysiloxanes having polar fluorinated grafts or pendant groups with hydrogen atoms attached to terminal difluoro-substituted carbon atoms. US2002/0016383 describes hydrophilic siloxane-based methacrylates containing ether and siloxane linkages and crosslinkable monomers containing polyether and polysiloxane groups. Any of the polysiloxanes described above may also be used as the silicone containing component in the present invention.

In one embodiment of the invention where a modulus of less than about 120psi is desired, a substantial portion of the mass fraction of the silicone-containing component used in the lens should contain only one polymerizable functional group ("monofunctional silicone-containing component"). In this embodiment, in order to ensure the desired balance of oxygen transmission rate and modulus, it is preferred that all components having more than one polymerizable functional group ("polyfunctional component") constitute no more than 10mmol/100g of reactive components, preferably no more than 7mmol/100g of reactive components.

In one embodiment, the silicone component is selected from monomethacryloxypropyl terminated mono-n-alkyl terminated polydialkylsiloxanes; bis-3-acryloxy-2-hydroxypropoxypropylpolydialkylsiloxane; (ii) a methacryloxypropyl-terminated polydialkylsiloxane; mono- (3-methacryloxy-2-hydroxypropoxy) propyl terminated mono-alkyl terminated polydialkylsiloxane; and mixtures thereof.

In one embodiment, the silicone component is selected from monomethacrylate terminated polydimethylsiloxanes; bis-3-acryloxy-2-hydroxypropoxypropylpolydialkylsiloxane; and mono- (3-methacryloxy-2-hydroxypropoxy) propyl terminated mono-butyl terminated polydialkylsiloxane; and mixtures thereof.

In one embodiment, the silicone component has an average molecular weight of about 400 to about 4000 daltons.

The silicone-containing component may be present in an amount up to about 95 wt.%, in some embodiments from about 10 to about 80 wt.%, and in other embodiments, from about 20 to about 70 wt.%, based on the total reactive components.

2-hydroxyethyl acrylamide (HEAA)

The reactive mixture also contains 2-hydroxyethyl acrylamide ("HEAA; structure in formula VIII).

As described in the examples below, HEAA was found to unexpectedly improve the cure speed and other properties of the resulting silicone polymers, silicone hydrogels, and/or biomedical devices (e.g., contact lenses) while still maintaining the transparency and transmittance of the articles made therefrom.

HEAA may be present in a wide range of amounts depending on the particular balance of properties desired. In one embodiment, the amount of hydrophilic component is up to about 50 weight percent, such as from about 5 to about 40 weight percent. In another embodiment, the HEAA is present in an amount up to about 10% by weight, in other embodiments from about 1 to about 10%.

Hydrophilic component

In one embodiment, the reactive mixture may also contain at least one hydrophilic component in addition to 2-hydroxyethyl acrylamide. In one embodiment, the hydrophilic component can be any of the hydrophilic monomers known to be useful in the preparation of hydrogels.

One class of suitable hydrophilic monomers includes acrylic-or vinyl-containing monomers. Such hydrophilic monomers may themselves serve as crosslinking agents, however, when hydrophilic monomers having more than one polymerizable functional group are used, their concentration should be defined as described above to provide a contact lens having the desired modulus.

The term "vinyl-type" or "vinyl-containing" monomer refers to a monomer containing a vinyl group (-CH ═ CH)₂) And monomers capable of polymerization.

Hydrophilic vinyl-containing monomers that can be incorporated into the silicone hydrogels of the present invention include, but are not limited to, monomers such as: n-vinyl amide, N-vinyl lactam (e.g., NVP), N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, and preferably NVP.

"acrylic-type" or "acrylic-containing" monomers are those monomers that contain an acrylic group: (CH)₂CRCOX) wherein R is H or CH₃And X is O or N, which are also known to be readily polymerizable, such as N, N-Dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), glycerol methacrylate, 2-hydroxyethyl methacrylamide, polyethylene glycol monomethacrylate, methacrylic acid, mixtures thereof, and the like.

Other hydrophilic monomers useful in the present invention include, but are not limited to, polyoxyethylene polyols in which one or more of the terminal hydroxyl groups is replaced with a functional group containing a polymerizable double bond. Examples include polyethylene glycol, ethoxylated alkyl glucosides, and ethoxylated bisphenol a, which are reacted with one or more equivalent weight end capping groups, such as isocyanatoethyl methacrylate ("IEM"), methacrylic anhydride, methacryloyl chloride, vinylbenzoyl chloride, and the like, to produce a polyethylene polyol having one or more terminal polymerizable olefinic groups bonded to the polyethylene polyol through linking moieties, such as urethane or ester groups.

Further examples are hydrophilic vinyl carbonate or vinyl carbamate monomers as disclosed in U.S. Pat. No. 5,070,215, and hydrophilic oxazolone monomers as disclosed in U.S. Pat. No. 4,910,277. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

In one embodiment, the hydrophilic component comprises at least one hydrophilic monomer, such as DMA, HEMA, glycerol methacrylate, 2-hydroxyethyl methacrylamide, NVP, N-vinyl-N-methacrylamide, polyethylene glycol monomethacrylate, and combinations thereof. In another embodiment, the hydrophilic monomer comprises at least one of DMA, HEMA, NVP, and N-vinyl-N-methacrylamide, and mixtures thereof. In another embodiment, the hydrophilic monomer comprises DMA and/or HEMA.

In another embodiment, the reaction mixture comprises at least one monomer having the formula

Wherein R is¹Is H or CH₃And R is²Is H or C1-6 alkyl.

The hydrophilic component (e.g., hydrophilic monomer) can be present in a wide range of amounts depending on the particular balance of properties desired. In one embodiment, the amount of hydrophilic component is up to about 60 weight percent, such as about 5 to about 40 weight percent.

Polymerization initiator

One or more polymerization initiators may be included in the reaction mixture. Examples of polymerization initiators include, but are not limited to, compounds that generate free radicals at moderately elevated temperatures (e.g., lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, and the like), and photoinitiator systems (e.g., aromatic alpha-hydroxy ketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphine oxides, and tertiary amines plus diketones, 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-trimethylpentylphosphine oxide (DMBAPO), bis (2,4, 6-trimethylbenzoyl) -phenylphosphine oxide (Irgacure819), 2,4, 6-trimethylbenzyldiphenylphosphine oxide and 2,4, 6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ester, and combinations of camphorquinone and ethyl 4- (N, N-dimethylamino) benzoate. Commercially available visible photoinitiator systems include, but are not limited to, Irgacure819, Irgacure1700, Irgacure1800, Irgacure819, Irgacure1850 (both from Ciba specialty Chemicals), and Lucirin TPO initiator (available from BASF). Commercially available UV photoinitiators include Darocur1173 and Darocur2959(Ciba Specialty Chemicals). These and other Photoinitiators that can be used are disclosed in photonitiators for freeradial Cationic & Anionic Photopolymerization, volume III, 2 nd edition, John Wiley and sons, edited by g.bradley, j.v.criville & k.dietliker; new York; 1998.

the polymerization initiator is used in the reaction mixture in an amount effective to initiate photopolymerization of the reaction mixture, such as from about 0.1 to about 2 weight percent. The polymerization of the reaction mixture may be initiated using an appropriate choice of heat or visible or ultraviolet light or other means, depending on the polymerization initiator used. Alternatively, initiation can be carried out without an initiator using, for example, an electron beam. However, when a photoinitiator is used, a preferred initiator is a bisacylphosphine oxide, such as bis (2,4, 6-trimethylbenzoyl) -phenylphosphine oxide (Irgacure)) Or 1-hydroxycyclohexyl phenyl ketone and bis (2, 6-dimethoxybenzoyl) -2, 4-4-trimethylpentylphosphine oxide (DMBAPO), in another embodiment, the method of polymerization initiation is via visible light activation. A preferred initiator is bis (2,4, 6-trimethylbenzoyl) -phenylphosphine oxide (Irgacure))。

Internal wetting agent

In one embodiment, the reaction mixture comprises one or more internal wetting agents. Internal wetting agents may include, but are not limited to, high molecular weight hydrophilic polymers (such as those described in U.S. Pat. Nos. 6,367,929; 6,822,016; 7786185; PCT patent applications WO03/22321 and WO 03/22322), or reactive hydrophilic polymers (such as those described in U.S. Pat. No. 7,249,848). Examples of internal wetting agents include, but are not limited to, polyamides such as poly (N-vinylpyrrolidone), poly (N, N-dimethylacrylamide), and poly (N-vinyl-N-methylacetamide). Other polymers such as hyaluronic acid, phosphorylcholine, and the like may also be used.

The internal wetting agent can be present in a wide range of amounts depending on the particular parameters desired. In one embodiment, the amount of wetting agent is up to about 50 weight percent, such as from about 5 to about 40 weight percent, such as from about 6 to about 40 weight percent.

Other Components

Other components that may be present in the reaction mixture used to form the contact lenses of the invention include, but are not limited to, compatibilizing components (such as those disclosed in U.S. patent application 2003/162862 and US 2003/125498), ultraviolet absorbing compounds, pharmaceutical agents, antimicrobial compounds, copolymerizable and non-polymerizable dyes, mold release agents, reactive tints, pigments, combinations thereof, and the like. In one embodiment, the sum of the additional components may be up to about 20 wt%. In one embodiment, the reaction mixture comprises up to about 18 wt.% of a wetting agent, and in another embodiment from about 5 to about 18 wt.% of a wetting agent.

Diluent

In one embodiment, reactive components (e.g., silicone-containing component, 2-hydroxyethyl acrylamide, hydrophilic monomer, wetting agent, and/or other components) are mixed together in the presence or absence of a diluent to form a reaction mixture.

In one embodiment, a diluent is used that is sufficiently low in polarity to solubilize the non-polar components of the reaction mixture under the reaction conditions. One way to characterize the polarity of the diluents of the present invention is via the Hansen solubility parameter p. In certain embodiments, p is less than about 10, preferably less than about 6. Suitable diluents are further disclosed in U.S. patent application 20100280146 and U.S. patent 6,020,445.

Classes of suitable diluents include, but are not limited to, alcohols having 2 to 20 carbon atoms, amides having 10 to 20 carbon atoms derived from primary amines, ethers, polyethers, ketones having 3 to 10 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. As the carbon number increases, the number of polar moieties may also increase to provide a desired level of water miscibility. In some embodiments, primary and tertiary alcohols are preferred. Preferred classes include alcohols having 4 to 20 carbon atoms and carboxylic acids having 10 to 20 carbon atoms.

In one embodiment, the diluent is selected from the group consisting of 1, 2-octanediol, t-amyl alcohol, 3-methyl-3-pentanol, decanoic acid, 3, 7-dimethyl-3-octanol, tripropylene methyl ether (TPME), butoxyethyl acetate, mixtures thereof, and the like.

In one embodiment, the diluent is selected from diluents having a degree of solubility in water. In some embodiments, at least about 3% of the diluent is miscible with water. Examples of water-soluble diluents include, but are not limited to, 1-octanol, 1-pentanol, 1-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3-dimethyl-2-butanol, decanoic acid, octanoic acid, dodecanoic acid, 1-ethoxy-2-propanol, 1-tert-butoxy-2-propanol, EH-5 (commercially available from Ethox Chemicals), 2,3,6, 7-tetrahydroxy-2, 3,6, 7-tetramethyloctane, 9- (1-methylethyl) -2,5,8,10,13, 16-hexaoxaheptadecane, 3,5,7,9,11, 13-hexamethoxy-1-tetradecanol, mixtures thereof, and the like.

Curing of silicone polymers/hydrogels and lens manufacture

The reaction mixture of the present invention may be cured via any known process for molding reaction mixtures used in the preparation of contact lenses, including rotary molding and static casting. Rotary die forming methods are disclosed in U.S. Pat. nos. 3,408,429 and 3,660,545, and static die casting methods are disclosed in U.S. Pat. nos. 4,113,224 and 4,197,266. In one embodiment, the contact lenses of the invention are formed by direct molding of silicone hydrogels, which is economical and enables precise control of the final shape of the hydrated lens. For this method, the reaction mixture is placed in a mold having the shape of the final desired silicone hydrogel, and the reaction mixture is subjected to conditions that polymerize the monomers, thereby producing a polymer having the approximate shape of the final desired product.

In one embodiment, after curing, the lens is subjected to extraction to remove unreacted components and release the lens from the lens mold. The extraction may be carried out using conventional extraction fluids, such as organic solvents, e.g. alcohols, or may be carried out using aqueous solutions.

The aqueous solution is a solution comprising water. In one embodiment, the aqueous solution of the present invention comprises at least about 30% by weight water, in some embodiments at least about 50% by weight water, in some embodiments at least about 70% water, and in other embodiments at least about 90% by weight water. The aqueous solution may also contain additional water soluble components such as mold release agents, wetting agents, slip agents, pharmaceutical and nutraceutical components, combinations thereof, and the like. The release agent is a compound or mixture of compounds that, when combined with water, reduces the time required to release a contact lens from a mold compared to the time required to release a lens using an aqueous solution that does not contain a release agent. In one embodiment, the aqueous solution comprises less than about 10 wt%, in other embodiments less than about 5 wt% of an organic solvent (such as isopropanol), and in another embodiment, the aqueous solution is free of organic solvents. In these embodiments, the aqueous solution does not require special treatment, such as purification, recycling, or special disposal procedures.

In various embodiments, extraction can be achieved, for example, via immersion of the lens in an aqueous solution, or exposure of the lens to a stream of aqueous solution. In various embodiments, the extraction may also include, for example, one or more of: heating the aqueous solution; stirring the aqueous solution; increasing the level of release aid in the aqueous solution to a level sufficient to release the lens; mechanically or ultrasonically agitating the lens; and incorporating at least one leaching aid into the aqueous solution to a level sufficient to facilitate sufficient removal of unreacted components from the lens. The foregoing may be conducted in a batch or continuous process with or without the addition of heat, agitation, or both.

Some embodiments may also include the application of physical agitation to facilitate leaching and demolding. For example, the lens mold part to which the lens is attached can be vibrated or moved back and forth within the aqueous solution. Other embodiments may include ultrasound passing through the aqueous solution.

The lenses may be sterilized by known means, including but not limited to autoclaving.

Contact lens Properties

It should be understood that all tests indicated herein have a certain amount of inherent test error. Thus, the results reported herein should not be taken as absolute values, but rather as ranges of values based on the accuracy of the particular test.

Oxygen permeability (Dk)

Oxygen permeability (or Dk) is measured as follows. Arranging the lens on the polarographic oxygen sensor, and then using a netThe upper side of the hole carrier is covered by the hole carrier, and the polarographic oxygen sensor consists of a gold cathode with the diameter of 4mm and a silver ring anode. The lenses were exposed to moist 2.1% O₂To the atmosphere of (c). Oxygen diffusion through the lens is measured by a sensor. The lenses are either stacked on top of each other to increase the thickness or thicker lenses are used. The L/Dk of 4 samples with distinctly different thickness values was measured and plotted against thickness. The reciprocal of the regression slope is Dk of the sample. Reference values are those measured on commercially available contact lenses using this method. Balafilcon A lenses (available from Bausch)&Lomb) provides a measurement of about 79 barrer. The Etafilcon lenses provide measurements of 20 to 25 barrer. (1barrer ═ 10^-10(cm of gas)³×cm²) /(cm of Polymer)³×sec×cm Hg))。

In one embodiment, the lens has an oxygen permeability of greater than about 50, such as greater than about 60, such as greater than about 80, such as greater than about 100.

Total Light transmittance (white Light transmittance)

The total light transmittance was measured using an SM color correction computer (model SM-7-CH, manufactured by Suga Test Instruments co. The lens sample was gently wiped of water and then the sample was placed in the light path and measured. The thickness was measured using an ABC number dial gauge (ID-C112, manufactured by Mitsutoyo Corporation), and samples having a thickness between 0.14 and 0.15mm were measured.

Modulus/elongation/toughness

The modulus (or tensile modulus) was measured by using a crosshead of constant velocity of a mobile tensile testing machine equipped with a load cell that was lowered to the initial gauge height. Suitable testing machines includeType 1122. Dog bone samples from a-1.00 diopter lens 0.522 inches long, 0.276 inches "ear" wide, and 0.213 inches "neck" wide were loaded into the grips and elongated at a constant rate of 2in/min until they broke. Initial meter for measuring sampleThe amount length (Lo) and the sample rupture length (Lf). At least five samples were measured for each composition and the average was recorded. The tensile modulus is measured at the initial linear portion of the stress/strain curve. In one embodiment, the tensile modulus is less than 400psi, such as less than 150psi, such as less than 125psi, such as less than 100 psi.

Percent elongation was measured using the following equation:

percent elongation ═ [ (Lf-Lo)/Lo ] × 100.

In one embodiment, the elongation is at least 100%, such as at least 150%, such as at least 200%, such as at least 250%.

The toughness of the material is calculated as follows: energy to destroy the material (E)_B) Divided by the rectangular volume of the sample (length × width × height.) energy to break the material (E)_B) The calculation is made from the area under the load/displacement curve.

Toughness ═ E_B/(Length × Width × height)

In one embodiment, the toughness is at least 100in lbf/in³E.g., at least 125in lbf/in³E.g. at least 150in lbf/in³。

Water content

The water content was measured as follows. The lenses to be tested were placed in the wetting solution for 24 hours. Each of the three test lenses was removed from the wetting solution using a sponge-end cotton swab and placed on an absorbent wipe that had been wetted with the wetting solution. Both sides of the lens are brought into contact with the wipe. Using forceps, the test lenses were placed in a weighing pan and weighed. Two additional sets of samples were prepared and weighed as above. The pan and lens were weighed three times and the average was wet weight.

The dry weight was measured by placing the sample pan in a vacuum oven preheated to 60 ℃ for 30 minutes. Vacuum was applied until at least 0.4 inches Hg was reached. The vacuum valve and pump were closed and the lenses were dried for 4 hours. And opening the air release valve to enable the oven to reach the atmospheric pressure. The pan was removed and weighed. The water content was calculated as follows:

wet weight-the weight of the combined wet-weight pan of pan and lens

Dry weight-combined dry weight of disc and lens-weight of the weighing disc

The mean and standard deviation of the water content of the samples were calculated and recorded. In one embodiment, the% water content is about 20 to 70%, such as about 30 to 65%.

Dynamic advancing contact Angle (DCA)

Advancing contact angles were measured as follows. A central strip was cut from an approximately 5mm wide lens and equilibrated in the wetting solution to produce four samples from each group. The wetting force between the lens surface and the borate buffered saline solution was measured using a Wilhelmy microbalance at 23 ℃ while the sample was immersed in the saline solution or pulled out of the saline solution. Using the following equation

F2 gamma pcos theta or theta cos^-1(F/2γp)

Where F is the wetting force, γ is the surface tension of the probe liquid, p is the sample perimeter at the meniscus, and θ is the contact angle. The advancing contact angle was obtained from the part of the wetting experiment when the sample was immersed in the wetting solution. Each sample was cycled 4 times and the results averaged to obtain the advancing contact angle of the lens.

Examples of the invention

These examples do not limit the invention. They are intended only to suggest a method of practicing the invention. Other methods of practicing the invention may be found by those familiar with contact lenses and other specialties. The following abbreviations are used in the following examples:

blue HEMA activity reaction product of blue 4 with HEMA, as described in example 4 of U.S. patent 5,944,853

DMA N, N-dimethylacrylamide

HEAA 2-HYDROXYETHYLAcrylamide

HEMA 2-hydroxyethyl methacrylate

Irgacure819 bis (2,4, 6-trimethylbenzoyl) -phenylphosphine oxide

Norbloc 2- (2' -hydroxy-5-methacryloyloxyethyl phenyl) -2H-benzotriazole

OH-mPDMS mono- (3-methacryloyloxy-2-hydroxypropoxy) propyl terminated mono-butyl terminated poly

Dimethylsiloxane (synthesis described in U.S. patent application 2008/0004383)

PVP poly (N-vinylpyrrolidone) (the K value)

TEGDMA tetraethyleneglycol dimethacrylate

TPME Triallylmethyl Ether

Example 1: hydrogel contact lens manufacture

A series of five blends were prepared using increasing amounts of HEAA instead of DMA (0%, 25%, 50%, 75% and 100%) and are shown in table 1 below. For each blend, all components were added to and mixed on a jar roller (jarroler) until all dissolved. All blends were clear.

Table 1: blend formulations

The amount of diluent is shown as a weight percentage of the combination of all components. The amounts of the other components are shown as weight percent of the reactive components except the diluent.

Blends 1-5 were placed in uncapped glass bottles in a nitrogen-filled glove box for at least 1 hour. A plastic contact lens mold filled one of the blends in a nitrogen filled glove box and was placed approximately 3 inches below a Philips TL0320W fluorescent bulb for 30 minutes. The lenses were cured at room temperature for 30 minutes in a nitrogen atmosphere. The lenses were leached as follows: firstly, in 50% isopropanol and 50% boric acid buffer salt solution for 30 minutes; then each in 100% isopropanol for 30 minutes for 3 cycles; then in 50% isopropanol 50% borate buffered saline solution for 30 minutes; finally 30 minutes each in 100% borate buffered saline for 3 cycles.

Example 2: all light transmittance test

Lenses were made from blends 2,3, 4 and 5 above, except that the blue HEMA was omitted. Lenses were tested using the full light transmittance test described above. The results are shown in table 2.

Example 3: mechanical Property testing

The resulting lenses of example 2 were subjected to Dk, DCA, water content and mechanical testing to determine the effect of adding HEAA instead of DMA on various lens properties.

Table 2: various lens properties

	Blend 1	Blend 2	Blend 3	Blend 4	Blend 5
						Water content (%)	43.5	44.7	45.2	43.8	45.1
Modulus (psi)	129.2	113.1	108.8	106.7	89.7
						Elongation (%)	188.1	198.6	224.3	260.3	310
Toughness (in lbf/in)3)	107.4	109.4	129.7	168.8	195.9
						DCA	72±10°	69±9°	79±5°	96±6°	90±12°
Dk(barrers)	96	98	101	95	105
						Total light transmittance (%)	NT	92.3	92.1	92.3	92.6

These results in table 2 show that the addition of HEAA unexpectedly reduced the modulus of the contact lenses (i.e., from 129.2 to 89.7psi), and also increased the elongation strength of the lenses (i.e., from 188.1 to 310%) and the toughness of the lenses (i.e., from 107.4 to 195.9). The lenses formed from blends 2 to 5 were all extremely clear with a total light transmission of about 92%. Comparing these lenses with those formed in comparative examples 1-6 of US2011/0230589, which have a transmission between 8.6 and 82%, lenses formed from the polymers of the present invention show significantly improved total light transmission.

Example 4: curing characteristics of HEAA-containing hydrogels

Curing properties of blend 1 (containing DMA) and blend 5 (containing HEAA) as shown above in table 1 were studied using a TA Instruments model Q100 photo-DSC equipped with a universal LED module from Digital Light laboratories model ULM-1-420. The sample was placed on a bench, purged with nitrogen, and equilibrated at 25 ℃ for 5 minutes first, then 70 ℃ for 5 minutes, and then the light curing process was initiated to provide 4mW/cm²。

The baseline was drawn using sigmoidal correction. Cure time was calculated using TA Universal Analysis2000 software. Enthalpy, cure time, and time to 25%, 50%, 75%, 90%, 95%, and 99.5% cure are shown in table 3. Each blend was tested several times and the values in the table represent the average from 3 to 4 tests.

Table 3: light curing results

These results show that the hydrogel with HEAA (blend 5) cured unexpectedly much faster than the hydrogel with DMA (blend 1). Furthermore, despite the reduced cure time, lenses made from blend 5 also unexpectedly exhibited lower modulus, increased elongation, and increased toughness, as shown in table 2.

Example 5: hydrogel contact lens manufacture

This example was designed to evaluate the effect of using HEAA instead of DMA on water content in standard silicone hydrogel lens blends. Two blends shown in table 4 were prepared as described in example 2. All blends were clear.

Table 4: blend formulations

Components	Blend 6 (% by weight)	Blend 7 (% by weight)
			OH-mPDMS	55.0	55.0
HEMA	8.0	8.0
			TEGDMA	3.0	3.0
Blue HEMA	0.04	0.04
			Norbloc	2.2	2.2
Irgacure819	0.14	0.14
			DMA	31.4	0.00
HEAA	0.00	31.4
			TPME (diluents)	45.01	45.01

The amount of diluent is shown as a weight percentage of the combination of all components. The amounts of the other components are shown as weight percent of the reactive components except the diluent.

Blends 6 and 7 were then fabricated into contact lenses as described in example 2. Lenses were also made from blend 7, but the blue HEMA was omitted. Their total light transmittance was measured and the results are shown in table 5.

Example 6: mechanical Property testing

The lenses made in example 5 were analyzed for DCA and water content. These results are given in table 5. The results show that HEAA unexpectedly increased the water content of the lenses.

Table 5: properties of the lens

	Blend 6	Blend 7
			Water content (%)	37.2	44.2
DCA	97±3°	99±8°
			Total light transmittance	NT	91.7

It should be understood that while the invention has been described in conjunction with specific embodiments thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the following claims. Other aspects, advantages, and modifications are within the scope of the claims.

Claims (17)

1. A silicone polymer having a total light transmittance of at least 90%, the polymer being formed from reactive components comprising (i) at least one silicone component and (ii) 2-hydroxyethyl acrylamide,

wherein the at least one silicone component is selected from bis-3-acryloxy-2-hydroxypropoxypropylpolydialkylsiloxanes; (ii) a methacryloxypropyl-terminated polydialkylsiloxane; mono- (3-methacryloxy-2-hydroxypropoxy) propyl terminated mono-alkyl terminated polydialkylsiloxane; and mixtures thereof, and

wherein the weight ratio of (i) the at least one silicone component to (ii) the 2-hydroxyethyl acrylamide is from 50:1 to 1:5,

wherein the silicone component is present in an amount of up to 95 weight percent based on the total reactive components,

wherein the reactive component further comprises at least one other hydrophilic acrylic-containing monomer,

wherein the at least one other hydrophilic acrylic-containing monomer is HEMA and/or DMA, and

wherein the amount of said 2-hydroxyethyl acrylamide and other hydrophilic acrylic-containing monomers is up to 60% by weight.

2. The polymer of claim 1, wherein the at least one silicone component is selected from the group consisting of monomethacryloxypropyl terminated mono-n-alkyl terminated polydialkylsiloxanes; bis-3-acryloxy-2-hydroxypropoxypropylpolydialkylsiloxane; and mono- (3-methacryloxy-2-hydroxypropoxy) propyl terminated mono-butyl terminated polydialkylsiloxane; and mixtures thereof.

3. The polymer of claim 1, wherein the at least one silicone component comprises a mono- (3-methacryloxy-2-hydroxypropoxy) propyl terminated mono-butyl terminated polydialkylsiloxane.

4. The polymer of claim 1, wherein 2-hydroxyethyl acrylamide is present in an amount up to 10 wt.%.

5. The polymer of claim 1, wherein the reaction mixture further comprises at least one monomer of the formula

Wherein R is¹Is H or CH₃And R is²Is H or C1-6 alkyl, and the monomer is not HEMA.

6. A silicone hydrogel comprising the silicone polymer of claim 1.

7. A silicone hydrogel formed from a reaction mixture comprising (i) at least one silicone component and (ii) 2-hydroxyethyl acrylamide,

wherein the at least one silicone component is selected from monomethacryloxypropyl terminated mono-n-alkyl terminated polydialkylsiloxanes; bis-3-acryloxy-2-hydroxypropoxypropylpolydialkylsiloxane; (ii) a methacryloxypropyl-terminated polydialkylsiloxane; mono- (3-methacryloxy-2-hydroxypropoxy) propyl terminated mono-alkyl terminated polydialkylsiloxane; and mixtures thereof, and

wherein the weight ratio of (i) the at least one silicone component to (ii) the 2-hydroxyethyl acrylamide is from 50:1 to 1:5,

wherein the silicone component is present in an amount of up to 95 weight percent based on the total reactive components,

wherein the reactive component further comprises at least one other hydrophilic acrylic-containing monomer,

wherein the at least one other hydrophilic acrylic-containing monomer is HEMA and/or DMA, and

wherein the amount of said 2-hydroxyethyl acrylamide and other hydrophilic acrylic-containing monomers is up to 60% by weight.

8. The hydrogel of claim 7, wherein the 2-hydroxyethyl acrylamide is present at a weight percentage of 1 to 25%.

9. The hydrogel of claim 7, wherein the reaction mixture further comprises a polyamide.

10. A contact lens comprising the polymer of claim 1.

11. A contact lens formed from the hydrogel of claim 7.

12. The contact lens of claim 10 wherein the contact lens has an elongation of at least 200%.

13. The contact lens of claim 11 wherein the contact lens has an elongation of at least 200%.

14. The contact lens of claim 10 wherein the contact lens has a modulus of less than 120 psi.

15. The contact lens of claim 11 wherein the contact lens has a modulus of less than 120 psi.

16. A biomedical device comprising the polymer of claim 1.

17. A biomedical device formed from the hydrogel of claim 8.