Intraocular lens materials and components

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62/173,877, filed June 10, 2015, which is incorporated herein by reference. This application also claims the benefit of U.S. Provisional Application No. 62/321,704, filed April 12, 2016, which is incorporated herein by reference.

This application is related to the following applications and patents: U.S. Patent No. 8,900,298, issued December 2, 2004; U.S. Patent Publication No. 2013/0131794, published May 23, 2013; and U.S. Patent No. 8,158,712, issued April 17, 2012, each of which is incorporated by reference herein.

References

All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

Presbyopia is a condition in which the eye loses its ability to focus on nearby objects. It is a natural part of aging and often becomes noticeable in people in their mid-40s, and the condition can continue to worsen until about age 65. In order for the eye to see nearby objects clearly, the refractive index of the ophthalmic lens needs to be increased or its shape needs to be more convex to improve focusing on nearby objects.

Cataracts are the leading cause of blindness and the most common eye disease worldwide, with visual impairment resulting in over 8 million doctor's visits per year. When cataract impairment impacts or alters an individual's activities of daily living, lens removal surgery with intraocular lens (IOL) implantation is the preferred method of treating the associated visual limitations. Approximately 2.5 million cataract surgeries are performed annually in the United States, making it the most common procedure for Americans over the age of 65. Each year, approximately 97 percent of cataract surgery patients receive an IOL implant, resulting in the annual cost of cataract surgery and related care in the United States exceeding $4 billion.

A cataract is defined as a clouding of a patient's lens, whether it is a localized opacity or a diffuse, global loss of transparency. However, to have clinical significance, a significant loss of vision or functional impairment must be caused by the cataract. Cataracts can occur as a result of aging or secondary to genetic factors, trauma, inflammation, metabolic or nutritional disorders, or radiation. Age-related cataract diseases are the most common.

In treating cataracts, surgeons remove the lens matrix from the capsular bag and replace it with an intraocular lens ("IOL") implant. A typical IOL provides a selected focal length that allows the patient to have fairly good distance vision. However, after cataract surgery, patients typically require reading glasses. This is explained by the imaging properties of the human eye, which are facilitated by several optical interfaces.

In addition to age-related loss of accommodation, such loss has also impacted IOLs for the treatment of cataracts. Although research into accommodative IOLs has yielded some success, the relative complexity and limited effectiveness of the methods and apparatus developed to date have hindered widespread commercialization of such devices.

Some intraocular lenses include an optical portion, one or more of which are polymeric. It may be desirable for the polymer to have properties that allow the intraocular lens to transform into a delivery shape that allows it to be implanted in the eye, and to return to its pre-implant shape after implantation in the eye. Additionally, it may be desirable for the polymer composition to have a sufficiently high refractive index.

Some intraocular lenses herein include a fluid therein, such as a silicone fluid. For example, some accommodative IOLs use fluid movement within the IOL or changes in fluid pressure within the IOL to produce refractive power changes during accommodation. When a fluid such as silicone oil is used within an intraocular lens, the fluid tends to swell into the bulk polymeric material of the intraocular lens over time. This can reduce the amount of silicone oil available to drive refractive power changes in the IOL. It is therefore desirable to minimize the amount of swelling into the bulk material. It is also important to provide a silicone oil that does not shorten the response time of the accommodative IOL. It would be desirable to match the polymer and/or fluid so that swelling of the fluid into the polymeric material is minimized or even prevented.

In IOLs that include different types of materials (e.g., cured polymer and silicone oil), it may be desirable to have the different types of materials substantially index matched (i.e., have the same or substantially the same index of refraction), and therefore it may also be beneficial to provide a fluid that has a refractive index as close as possible to that of the bulk polymer material.

<p><patcit num="1"><text>U.S. Patent No. 7,276,619</text></patcit></p>

<p>One aspect of the present disclosure is an intraocular lens comprising a polymeric material including butyl acrylate present in an amount between 2% and 20%, trifluoroethyl methacrylate present in an amount between 10% and 35%, and phenylethyl acrylate present in an amount between 50% and 80%.</p><p>In some embodiments, the refractive index of the polymeric material is between 1.48 and 1.53, In some embodiments, the refractive index of the polymeric material is between 1.50 and 1.53.</p><p>In some embodiments, the polymeric material defines a fluid channel, and the intraocular lens further comprises a silicone oil in the fluid channel. In some embodiments, the silicone oil is index matched to the polymeric material. In some embodiments, the silicone oil has a polydispersity of less than 1.2.</p><p>One aspect of the present disclosure is a polymeric material for an ophthalmic device comprising: an alkyl acrylate present in an amount between 3% and 20%; a fluoroacrylate present in an amount between 10% and 35%; and a phenyl acrylate present in an amount between 50% and 80%.</p><p>One aspect of the present disclosure is an accommodating intraocular lens comprising an optic portion comprising a polymeric material adapted to refract light onto the retina; and a silicone oil having a polydispersity index of less than about 1.2 disposed within the optic portion.</p><p>In some embodiments, the silicone oil has an average molecular weight of 4500-6500.</p><p>In some embodiments, the viscosity is less than or equal to 2400 cP.</p><p>In some embodiments, the silicone oil comprises diphenylsiloxane units.</p><p>In some embodiments, the silicone oil is made from a cyclotrisiloxane containing a ratio of two dimethylsiloxane units to one diphenylsiloxane unit.</p><p>In some embodiments, the refractive index of the silicone oil is from 1.47 to 1.53, optionally from 1.50 to 1.53.</p><p>One aspect of the present disclosure is an adhesive for an accommodating intraocular lens, the adhesive including a first component having the same or substantially similar properties as a polymeric material of a first object of the accommodating intraocular lens.</p><p>In some embodiments, the adhesive comprises a first component that is the same as the polymeric material of the first object of the intraocular lens, hi some embodiments, the adhesive comprises a first component that comprises a monomer present in the polymeric material.</p><p>In some embodiments, the adhesive includes a second main component that is a reactive acrylic diluent.</p><p>In some embodiments, the adhesive comprises a first component that is substantially similar, but not the same, as the polymeric material of the first object of the accommodating intraocular lens.</p><p>One aspect of the present disclosure is a method of manufacturing an accommodating intraocular lens, the method comprising: curing first and second components of the accommodating intraocular lens; and applying an adhesive between the first and second components, the adhesive comprising a first component having the same, substantially the same, or substantially similar properties as at least one of the first and second components, and further comprising a second main component that is a reactive acrylic diluent.</p><p>One aspect of the present disclosure is a method of making a polymer component of an intraocular lens comprising a plurality of monomers, the method comprising the steps of: forming a polymer prepolymer comprising the plurality of monomers; and curing the prepolymer to form the polymer component.</p><p>In some embodiments, forming the prepolymer comprises combining a plurality of monomers with a monomer comprising a hydroxyl moiety. The method may further comprise forming a crosslinkable polymer from the prepolymer, the crosslinkable polymer comprising converting the hydroxyl moieties to methacrylate moieties.</p>

<figref num="1A">FIG. 1 illustrates an exemplary accommodating intraocular lens.</figref><figref num="1B">FIG. 1 illustrates an exemplary accommodating intraocular lens.</figref><figref num="1C">FIG. 2 is a cross-sectional view of the accommodating intraocular lens of FIGS. 1A and 1B.</figref><figref num="1D">FIG. 2 is a top view of an exemplary posterior element of an accommodating intraocular lens.</figref><figref num="1E">1 is a cross-sectional assembly view of an exemplary optic portion of an accommodating intraocular lens.</figref><figref num="2A">1A-1C illustrate deformations of an exemplary support in response to an exemplary force.</figref><figref num="2B">1A-1C illustrate deformations of an exemplary support in response to an exemplary force.</figref><figref num="3">FIG. 2 illustrates the curing process.</figref><figref num="4">FIG. 2 illustrates the synthesis of a prepolymer.</figref><figref num="5">FIG. 1 illustrates an exemplary hydrophilic material.</figref><figref num="6">FIG. 1 illustrates the formation of cross-linked polymers and exemplary adhesive designs.</figref>

The present disclosure generally relates to intraocular lenses, optionally accommodating intraocular lenses, and to exemplary materials and their properties for imparting desired properties to the intraocular lenses. The intraocular lenses herein are merely examples of intraocular lenses that may include any of the materials herein, and the disclosure is in no way limited to the exemplary intraocular lenses herein.

In some embodiments, the intraocular lens is an accommodating intraocular lens that is adapted to be placed in the natural lens capsule after the natural lens has been removed. In some embodiments, the peripheral non-optical portion (i.e., the portion not specifically adapted to focus light on the retina) can be adapted to respond to deformation of the lens capsule due to relaxation and contraction of the ciliary muscle. The response is deformation of the peripheral portion causing fluid disposed in the non-optical and optic portions to move between the peripheral portion and the optic portion, changing the optical parameters (e.g., optical power) of the intraocular lens. These embodiments are merely examples of intraocular lenses, optionally accommodating, that include any of the materials or are manufactured using any of the methods herein.

FIG 1A is a top view of a merely exemplary accommodating intraocular lens 10 including an optic 12 and a peripheral portion including, in this embodiment, first and second haptics 14 coupled to and extending peripherally from the optic 12. The optic 12 is adapted to refract light entering the eye onto the retina. The haptics 14 are configured to engage the capsular bag and are adapted to deform in response to deformation of the capsular bag associated with the ciliary muscle. FIG 1B is a perspective view of the intraocular lens 10 showing the optic 12 and the haptics 14 coupled to the optic 12.

The haptics are in fluid communication with the optic. Each haptic has a fluid chamber in fluid communication with the optic chamber in the optic. The haptics are formed of a deformable material and adapted to engage the lens capsule and deform in response to deformation of the lens capsule associated with the ciliary muscle. Deformation of the haptics changes the volume of the haptics fluid chamber, causing fluid disposed in the haptics and optic fluid chambers to move from the haptics fluid chamber into the optic fluid chamber or from the optic fluid chamber into the haptics fluid chamber. When the volume of the haptics fluid chamber decreases, fluid moves into the optic fluid chamber. When the volume of the haptics fluid chamber increases, fluid moves from the optic fluid chamber into the haptics fluid chamber. The flow of fluid into and out of the optic fluid chamber changes the configuration of the optic and the refractive power of the intraocular lens.

FIG. 1C is a side cross-sectional view through section AA shown in FIG. 1A. The optic 12 includes a deformable anterior element 18 secured to a deformable posterior element 20. Each haptic 14 includes a fluid chamber 22 in fluid communication with the optic fluid chamber 24 of the optic 12. Only the bond between the haptic 14 and the optic 12 on the left side of the figure is shown (but is obscured) in the cross-sectional view of FIG. 1C. The haptic fluid chamber 22 on the left side of the figure is shown in fluid communication with the optic fluid chamber 24 by two openings 26 formed in the posterior element 20. The haptic 14 on the right side of FIG. 1C is in fluid communication with the optic chamber 24 by two further openings (not shown) also formed in the posterior element at substantially 180 degrees from the openings shown.

FIG. 1D is a top view of the posterior element 20 (anterior element 18 and haptics 14 not shown). The posterior element 20 includes buttress portions 29 having a channel 32 formed therein. The channel 32 provides fluid communication between the optic 12 and the haptics 14. The opening 26 is disposed at one end of the channel 32. Thus, the optic fluid chamber 24 is in fluid communication with one haptic by two fluid channels. The buttress portions 29 are configured and sized to be disposed within an opening formed in the haptics 14 that defines one end of the haptic fluid chamber, as described below. Each of the buttress portions 29 includes two channels formed therein. The first channel of the first buttress is aligned with the first channel of the second buttress. The second channel of the first buttress is aligned with the second channel of the second buttress.

FIG. 1E is a side assembled view of section AA of the optic 12 including the anterior element 18 and the posterior element 20 (with haptics not shown for clarity). The inclusion of the fluid channel 32 in the posterior element 20 requires that the posterior element 20 have sufficient structure within which the channel 32 can be formed. The buttress portion 29 provides a structure within which the channel 32 can be formed. At its outermost portion, the posterior element 20 is higher than the anterior element 18 in the anterior-to-posterior direction. In alternative embodiments, the channel may be formed in the anterior element 18 rather than the posterior element 20. The anterior element would include the buttress portion 29 or other similar structure to provide a structure within which the channel can be formed. In these alternative embodiments, the posterior element may be formed similarly to the anterior element 18.

As shown in FIG. 1E, the rear element 20 is secured to the front element 18 at a peripheral surface 28, which is a flat surface around the periphery of the rear element 20. The elements 18 and 20 can be secured to each other using any of the known biocompatible adhesives or adhesives described elsewhere herein and any of the known methods or methods for bonding the first and second members herein. The front element 18 and the rear element 20 can also be formed from a single material to eliminate the need to secure the two elements to each other. In some embodiments, the diameter of the area where the front element 18 and the rear element 20 are secured to each other is about 5.4 mm to about 6 mm in diameter.

The haptics (or other type of peripheral portion if a separate member) can be adhered to the optic using any of the adhesives described herein or any of the methods described herein for adhering the first and second members together.

2A and 2B simply illustrate the placement of an accommodating intraocular lens (as shown in FIGS. 1A-1E) in the eye and how it may respond to ciliary muscle movement. The deformation of at least a portion of the intraocular lens, and the responsiveness of the fluid therein, is influenced by the material selected for the AIOL and is shown in FIGS. 2A and 2B. The elastic lens capsule "CB" is connected to the zonules "Z", which are connected to the ciliary muscle "CM". As shown in FIG. 2A, when the ciliary muscle relaxes, the zonules stretch. This stretch pulls the capsule in a generally radially outward direction due to a radially outward force "R" due to the generally equatorial nature of the connection between the capsule and the zonules. The stretching of the zonules results in an overall stretching of the capsule, thinning it. When the natural lens is still present within the capsule, it becomes flatter (in the anterior to posterior direction) and radially higher, which reduces the refractive power of the lens. Relaxation of the ciliary muscle, as shown in FIG. 2A, results in distance vision. However, when the ciliary muscle contracts, as occurs when the eye attempts to focus on a nearby object, the radially inner portion of the muscle moves radially inward, causing the zonules to relax. This is shown in FIG. 2B. Relaxation of the zonules causes the capsule to move toward a generally more curved shape, with an anterior surface having a higher curvature than the unaccommodated shape, which provides a higher refractive power and allows the eye to focus on nearby objects. This is commonly referred to as "accommodation" and the lens is said to be in an "accommodating" shape.

The radially outer portion 42 is merely an exemplary portion of the haptic that directly engages the portion of the capsule that is connected to the zonules. The haptic outer portion 42 is adapted to respond to a generally radially applied capsule deformation force "R" when the zonules relax and stretch. This allows the haptic to deform in response to forces associated with the ciliary muscle (i.e., capsule contraction and relaxation), resulting in fluid flow between the haptic and optic in response to ciliary muscle relaxation and contraction. This is shown in FIG. 2B. When the ciliary muscle contracts (FIG. 2B), the peripheral region of the elastic capsule deforms and exerts a radially inward force "R" on the radially outer portion 42 of the haptic 14. The radially outer portion 42 is adapted to deform in response to this capsule deformation. The deformation reduces the volume of the fluid channel 22, forcing fluid from the haptic chamber 22 to the optic chamber 24. This increases the fluid pressure in the optic chamber 42. The increase in fluid pressure causes the flexible anterior element 18 and the flexible posterior element 20 to deform, increasing their curvature, and thus increasing the optical power of the intraocular lens.

The accommodating intraocular lenses herein may also be adapted to be placed outside the natural lens capsule, for example, the accommodating intraocular lenses may be adapted to be placed in front of, or at the anterior portion of, the capsule after the natural lens has been removed or while the natural lens is still in the capsule, where the peripheral portion of the lens is adapted to respond directly to the ciliary muscle rather than relying on deformation of the capsule.

The intraocular lenses described herein, such as the accommodating intraocular lenses depicted in Figures 1A-1E, may have one or more components that are polymeric. For example, in the examples of Figures 1A-1E, the anterior and posterior components may be polymeric materials. The peripheral portions (e.g., haptics) may also be polymeric.

The polymeric material has improved resistance to fluid diffusion, a relatively high refractive index, and is adapted to assume an initial shape after being deformed during implantation in the human body. Although the polymeric material can be used in a variety of applications, the polymers are described herein in their use in ophthalmic devices such as intraocular lenses ("IOLs"). One use of the polymers is in fluid-driven, accommodative IOLs, although the polymers can be used in non-accommodative or non-fluid-driven IOLs. In addition to IOLs, the polymeric compositions of the present invention can also be used in other ophthalmic devices, such as, but not limited to, contact lenses, artificial corneas, capsular expansion rings, corneal inlays, corneal rings, or other ophthalmic devices. Another exemplary use is in the field of breast implants, where the polymers can be used as an outer shell-like material to prevent the inner material from leaking.

The polymer compositions described herein may be used in IOLs, such as any of the fluid-driven IOLs described in U.S. patent application Ser. No. 60/433,046, filed Dec. 12, 2002; U.S. patent application Ser. No. 10/734,514, filed Dec. 12, 2003; U.S. patent application Ser. No. 10/971,598, filed Oct. 22, 2004; U.S. patent application Ser. No. 11/173,961, filed July 1, 2005; U.S. patent application Ser. No. 11/252,916, filed Oct. 17, 2005; U.S. patent application Ser. No. 11/642,388, filed Dec. 19, 2006; and U.S. patent application Ser. No. 11/646,913, filed Dec. 27, 2006, the disclosures of which are incorporated herein by reference in their entireties. However, the compositions may also be used in non-fluid-driven or non-accommodating IOLs.

Devices implanted in the eye become exposed to fluids within the eye. Fluids within the eye can diffuse through the device over time and have unintended and/or undesirable effects on the physical properties of the device. For example, polymeric IOLs implanted in the eye can suffer from the diffusion of ocular fluids into the polymeric material of the IOL. Attempts have been made to coat ocular devices with barrier layers to prevent such diffusion, but these methods can be expensive and time consuming. Furthermore, if the ocular device contains a chamber or channel within the device that contains fluid, there is a risk that the fluid may diffuse out of the fluid chamber and into the polymeric material. This not only reduces the amount of fluid available to the IOL, but also potentially changes the physical properties of the polymeric material. Thus, the bulk polymers of the present invention described herein may be used in ocular devices to resist the diffusion of fluids into or out of the device.

For implantable devices that must be implanted through a scleral incision, it is generally desirable for the scleral incision to be as small as possible while still being able to deform the device without damaging it.The device must also be able to deform to its initial shape after delivery.Thus, the polymers of the present invention described herein can be used in ophthalmic devices that need to be deformed to be delivered through an incision, but will return to their initial shape as soon as they are implanted in the eye.

Similarly, it may be desirable to increase the refractive index ("RI") of an ophthalmic device to increase its optical power. Increasing the RI of the bulk polymer may allow the device to be made thinner, while maintaining the desired optical power. This may also provide a device with a smaller profile upon delivery to reduce the size of the incision in the eye during implantation.

The improved properties of the polymers described herein include, but are not limited to, elastic modulus, refractive index, resistance to fluid diffusion, compositional responsiveness, mechanical strength, stiffness, wettability, and optical clarity. These properties are not necessarily mutually exclusive, and the list is not intended to be exhaustive.

Some embodiments of the present disclosure include a polymeric material for an ophthalmic device. The polymer comprises a first component, a second component, and a third or further component. In a preferred embodiment, the composition comprises butyl acrylate, trifluoroethyl methacrylate, phenylethyl acrylate, and a crosslinker, such as ethylene glycol dimethacrylate. These monomers are not intended to be limiting and are provided by way of example.

To obtain desired properties of the polymer, it is contemplated that particular monomers or other components may be selected to provide the particular properties, or particular monomers and other components may be selected in combination to provide the particular properties.

For example, butyl acrylate, a rubbery material, generally increases the responsiveness of polymeric materials. Alternatives to butyl acrylate include alkyl acrylates and other monomers with suitable responsive properties. Alternatives to butyl acrylate that can exhibit responsive properties include, but are not limited to, octyl acrylate, dodecyl methacrylate, n-hexyl acrylate, n-octyl methacrylate, n-butyl methacrylate, n-hexyl methacrylate, n-octyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, 2,2-dimethylpropyl acrylate, 2,2-dimethylpropyl methacrylate, trimethylcyclohexyl acrylate, trimethylcyclohexyl methacrylate, isobutyl acrylate, isobutyl methacrylate, isopentyl acrylate, isopentyl methacrylate, and mixtures thereof. Additionally, alternatives to butyl acrylate can include branched alkyl esters such as 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, 2,2-dimethylpropyl acrylate, 2,2-dimethylpropyl methacrylate, trimethylcyclohexyl acrylate, trimethylcyclohexyl methacrylate, isobutyl acrylate, isobutyl methacrylate, isopentyl acrylate, isopentyl methacrylate, and mixtures thereof.

In some embodiments, butyl acrylate is present in the range of about 10% to about 80% by volume, and in some embodiments, in the range of about 20% to about 70% by volume. In preferred embodiments, butyl acrylate is present in the range of about 35% to about 65% by volume, and in more preferred embodiments, in the range of about 45% to about 65% by volume. All percentages recited herein are considered to be "by volume" unless specifically stated otherwise.

In some embodiments, the polymer has an elastic modulus in the range of about 0.1 to about 0.6 MPa, hi some embodiments, the elastic modulus is about 0.1 to about 0.3 MPa.

Trifluoroethyl methacrylate, or a suitable alternative, may be added to the polymeric material to increase the resistance of the polymer to the diffusion of fluids as described herein. In general, the use of monomers with more fluorine atoms will increase the resistance of the polymer to the diffusion of fluids.

Although the ethyl group of trifluoroethyl can optionally bond up to five fluorine atoms, a large number of fluorine atoms can reduce the refractive index of the polymer. Thus, in some embodiments, trifluoroethyl methacrylate provides a desirable balance between the polymer's resistance to diffusion and the polymer's refractive index.

Fluorocarbon monomers can increase the resistance of the polymer to fluid diffusion, and some can be used as replacements for trifluoroethyl methacrylate. Alternatives to trifluoroethyl methacrylate include fluoroacrylates and other monomers that provide polymers with suitable resistance to diffusion properties. Alternatives to trifluoroethyl methacrylate include, but are not limited to, heptadecafluorodecyl acrylate, heptadecafluorodecyl methacrylate, hexafluorobutyl acrylate, hexafluorobutyl methacrylate, tetrafluoropropyl methacrylate, octafluoropentyl acrylate, octafluoropentyl methacrylate, dodecafluoroheptyl methacrylate, heptafluorobutyl acrylate, trifluoroethyl acrylate, hexafluoroisopropyl methacrylate, pentafluorophenyl acrylate, and pentafluorophenyl methacrylate.

In some embodiments, trifluoroethyl methacrylate is present in the range of about 5% to about 70%, and in some embodiments, it is present in the range of about 10% to about 50%. In preferred embodiments, it is present in the range of about 15% to about 30%, and in more preferred embodiments, it is present in the range of about 18% to about 22%.

Phenylethyl acrylate, or a suitable alternative, may be included in the polymer composition to increase the refractive index of the polymer. Phenyl groups generally can increase the refractive index of a polymer. Alternatives to phenylethyl acrylate include phenyl acrylate and other monomers that provide a polymer with a suitably high refractive index.

Other groups that can be used to increase the refractive index of the polymer include, but are not limited to, benzyl (benzoyl), carbazol-9-yl, tribromophenyl, chlorophenyl, and pentabromophenyl. Exemplary monomers that can be used to replace phenylethyl acrylate include, but are not limited to, tribromophenyl acrylate, 2-(9H-Carbazolyl-9-yl)ethyl methacrylate, 3-chlorostyrene, 4-chlorophenyl acrylate, benzyl acrylate, benzyl methacrylate, benzyl methacrylamide, n-vinyl-2-pyrrolidone, n-vinylcarbazole, pentabromophenyl acrylate, and pentabromophenyl methacrylate, phenylethyl methacrylate, 2-phenylpropyl acrylate, or 2-phenylpropyl methacrylate.

In some embodiments, phenylethyl acrylate is present in the range of about 5% to about 60%, while in some embodiments, it is present in the range of about 10% to about 50%. In preferred embodiments, it is present in the range of about 20% to about 40%, and in more preferred embodiments, it is present in the range of about 26% to about 34%.

In some embodiments, the refractive index of the polymer is from about 1.44 to about 1.52. In some embodiments, the refractive index is from about 1.47 to about 1.52. In some embodiments, the refractive index is from about 1.47 to about 1.5.

In some embodiments, the composition also includes a crosslinking agent such as ethylene glycol dimethacrylate. Examples of suitable crosslinking agents include, but are not limited to, diacrylates and dimethacrylates of triethylene glycol, butylene glycol, neopentyl glycol, ethylene glycol, hexane-1,6-diol, and thio-diethylene glycol, trimethylolpropane triacrylate, N,N'-dihydroxyethylenebisacrylamide, diallyl phthalate, triallyl cyanurate, divinylbenzene; ethylene glycol divinyl ether, N,N'-methylene-bis-(meth)acrylamide, sulfonated divinylbenzene, divinyl sulfone, ethylene glycol diacrylate, 1,3-butanediol dimethacrylate, 1,6 hexanediol diacrylate, tetraethylene glycol dimethacrylate, trifunctional acrylates, trifunctional methacrylates, tetrafunctional acrylates, tetrafunctional methacrylates, and mixtures thereof.

The crosslinker may be present in an amount of less than about 10%, less than about 5%, less than about 2%, or less than about 1%. The crosslinker allows the polymer to interweave in three-dimensional space, resulting in a compact molecular structure with improved elastic memory or response over non-crosslinked compositions.

In some embodiments of the present invention, the polymer composition also includes one or more ultraviolet (UV) light absorbing materials, such as acrylate or methacrylate functionalized benzotriazoles or benzophenones, in an amount of less than about 5%. In some embodiments, the UV absorbing materials are present in the range of about 0.05% to about 2%. UV absorbers suitable for use in the present invention include, but are not limited to, β-(4-benzotriazoyl-3-hydroxyphenoxy)ethyl acrylate, 4-(2-acryloyloxyethoxy)-2-hydroxybenzophenone, 4-methacryloyloxy-2-hydroxybenzophenone, 2-(2'-methacryloyloxy-5'-methylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methacryloyloxyethylphenyl)-2H-benzotriazole, 2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropyl)phenyl]-5- chloro-benzotriazole, 2-[3'-tert-butyl-5'-(3''-dimethylvinylsilylpropoxy)-2'-hydroxyphenyl]-5-m-ethoxybenzotriazole, 2-(3'-allyl-2'-hydroxy-5'-methylphenyl)benzotriazole, 2-[3'-tert-butyl-2'-hydroxy-5-(3''-methacryloyloxypropoxy)phenyl]-5-chloro-benzotriazole, and 2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropoxy)phenyl]-5-chloro-benzotriazole. Those skilled in the art will recognize that various other chemicals of the UV absorber may be selected.

One or more suitable free radical thermal polymerization initiators may be added to the polymer composition described herein. Examples of such initiators include, but are not limited to, organic peroxides, such as acetyl peroxide, lauroyl peroxide, decanoyl peroxide, stearoyl peroxide, benzoyl peroxide, tert-butyl peroxypivalate, peroxydicarbonate, etc. Such initiators may be added in the range of about 0.01% to about 1% of the total polymer mixture.

Alternative UV initiators include those known in the art, such as, but not limited to, benzoin methyl ether, benzoin ethyl ether, Darocur® 1173, 1164, 2273, 1116, 2959, 3331 (EM Industries), and Irgacur® 651 and 184 (Ciba-Geigy, Basel, Switzerland).

The diffusion resistance of the polymers of the present invention described herein may be further enhanced by providing a barrier layer on the outer surface of the ophthalmic device. Furthermore, if the device includes a fluid chamber disposed within the device (such as a fluid chamber disposed within a fluid-driven accommodative IOL), the device may also have a barrier layer on the inner surface of the fluid chamber to enhance resistance to diffusion from the fluid chamber. The barrier layer may be a thin layer of a fluorocarbon material or polymer, examples of which include hexafluoroethane, hexafluoropropylene, hexafluoropropane, octafluoropropane, polytetrafluoroethylene, and 1H,1H,2H-perfluoro-1-dodecene. The barrier layers may be attached or covalently bonded onto the solid surface of the ophthalmic device, either individually or in combination by various manufacturing processes. One common manufacturing process is plasma deposition.

The layers formed by plasma deposition are typically very thin, for example about 20 to about 100 nanometers. Fluorocarbon polymers generally have a low refractive index, so barrier layers with thicknesses less than one-quarter of the wavelength of visible light are invisible to the naked eye.

As mentioned above, the polymers of the invention described herein may be used in IOLs having a fluid disposed therein, such as in a fluid chamber. In general, the viscosity of a fluid is related to the diffusion properties of the fluid. Fluids with low viscosity can diffuse through a polymer more easily.

The ophthalmic device may contain silicone oil. The amount of silicone oil diffusing through the polymer can be reduced by selecting a silicone oil with a narrow molecular weight distribution, particularly by removing low molecular weight silicone oil molecules. A series of stripping methods are commonly used to remove low molecular weight components in silicone oil. In general, low molecular weight components will diffuse faster than high molecular weight components. However, high molecular weight components contribute to increased viscosity, which requires more force to pump the fluid through the IOL. Therefore, silicone oils with narrow molecular weight distribution are preferred. The fluid placed in the ophthalmic device is not limited to silicone oil, and may be, for example, saline.

However, in some embodiments, the IOL members are substantially index matched so that the deflection of one of the IOL's surfaces contributes significantly to any change in optical power during accommodation. For example, the bulk polymer will be substantially index matched to any fluid in the IOL. Substantially index matched, as the term is used herein, includes small differences in refractive index between the members of the IOL. For example, if adhesives are used in the manufacture of the IOL, they may have different refractive indices, but the difference will be negligible when considering the overall optical power change of the accommodative IOL.

In some embodiments, the T of the polymer_GAt approximately -20°C, it can stretch to about four times its length without breaking.

The optic and haptics may be composed of the same polymer composition or different compositions. The composition of the optic and haptics may depend on what properties are desired in each of the components. For example, it may not be necessary to achieve a high refractive index in the haptics since they generally do not contribute to focusing light, so the polymer used for the haptics may not require a high refractive index. Similarly, for example, it may be desirable for the haptics to have a different response than the static optic.

The following non-limiting examples illustrate certain aspects of the invention.

Example 1

Add the following ingredients together and mix well.

<tables><img file="JP2024166312A_D0001.tif" /></tables>

The polymer can be produced by pouring the formulation into a mold and curing the polymer by either UV or thermal curing. The resulting polymer had a swelling index of 0 in silicone oil, a refractive index of 1.477, and an elastic modulus of 0.163 Mpa.

Example 2

The following formulations can be added together, mixed well, and processed in the same manner as the formulation in Example 1.

<tables><img file="JP2024166312A_D0002.tif" /></tables>

The swelling ratio of the resulting polymer was 0.019, the refractive index was 1.473, and the elastic modulus was 0.27 Mpa.

While the above embodiments have shown exemplary polymer formulations, further exemplary formulations having higher refractive indices than those shown above are shown below. Increasing the refractive index may be desirable to increase the base optical power of the intraocular lens. In some embodiments, the refractive index of the polymeric material of the intraocular lens is about 1.48 to about 1.53, and in some cases 1.50 to 1.53. The refractive index of the bulk polymer may be increased by increasing the concentration of phenylethyl acrylate as a weight percent of the polymer. Other components may be modified to offset the increased concentration of monomers containing phenyl groups. Table 1 below shows further exemplary polymer formulations for use in ophthalmic devices and components thereof, where the refractive index is higher than some of the above embodiments. The first three formulations have refractive index values very close to 1.5180 at 532 nm and 35° C., which are examples of RIs between 1.50 and 1.53. The fourth formulation is similar to some of the above examples. All four formulations in Table 1 include BA, PEA, and TFEMA.

A typical and important advantage of the exemplary formulations of Table 1 (including their relatively high refractive index) is that they have a dramatically reduced tendency to swell when exposed to silicone fluids commonly used in some fluid-driven accommodating intraocular lenses, such as those incorporated herein by reference. The data supports the reduced swelling, which manifests itself as significantly improved optical power stability and the potential ability to perform accelerated aging studies without the loss of optical power due to swelling seen in some fluid-driven accommodating intraocular lenses.

<tables><img file="JP2024166312A_D0003.tif" /></tables>

Formulations 1-3 in Table 1 can be used, for example, in the optic portion of an accommodating intraocular lens ("AIOL") (accommodating intraocular lenses are fluid-driven), or in the peripheral portion of an AIOL.

The specific monomers shown herein are merely examples, and the scope of the present disclosure is not so limited. For example, in some embodiments, the percentage of BA is 2-20%, such as 3-17%. In some embodiments, the percentage of PEA is 50-80%, such as 60-75%. In some embodiments, the percentage of TFEMA is 10-35%, such as 15-30%.

The first three formulations in Table 3 are also examples of polymeric materials that include an alkyl acrylate present in an amount between 3% and 20%, a fluoroacrylate present in an amount between 10% and 35%, and a phenyl acrylate present in an amount between 50% and 80%.

Various manufacturing processes can be used to produce the polymeric material, including curing. Figure 3 shows an exemplary method of curing three monomers (i.e., BA, PEA, and TFEMA), a UV blocker, and a crosslinker, such as EGDMA, to obtain a cured polymeric material containing the three monomers. Any of the polymeric materials can be produced in this manner.

FIG. 4 illustrates an alternative manufacturing process, where a prepolymer is first made with multiple monomers (in this example, they are the same as in FIG. 3, but need not be the same), and as shown in FIG. 4, the prepolymer is not yet crosslinked (not yet fully cured). The monomer is first combined with a monomer containing a hydroxyl moiety, which is then converted to a crosslinkable methacrylate, which allows the crosslinkable polymer to be fully cured. In some embodiments, the monomer containing a hydroxyl moiety is a methacrylate (e.g., hydroxyethyl methacrylate ("HEMA")) or an acrylate (e.g., hydroxyethyl acrylate ("HEA"), hydroxybutyl acrylate ("HBA")). HEMA is used in the illustrative FIG. 4. FIG. 6A illustrates an exemplary method of making a crosslinkable polymer from a prepolymer (such as the prepolymer of FIG. 4), where the hydroxyl moiety is converted to a methacrylate (bottom right of FIG. 6A), which can then be crosslinked to form a cured polymeric material that can be used to make any of the components of any of the illustrative IOLs herein.

As described in more detail with respect to the adhesive discussion (fully incorporated in this section of the disclosure), crosslinkable polymers such as those listed above can be combined with hydrophilic reactive diluents. When hydrophilic monomers (e.g., HEMA, HBA) are used as reactive diluents in the crosslinkable polymer, curing results in an interpenetrating network in the polymer matrix that includes a hydrophilic homopolymer as a second phase. Long chain homopolymer "blocks" can increase the availability of functional groups associated with the hydrophilic component in the random copolymer. In some embodiments, polymers are developed by using about 25-35% (e.g., 30%) HEMA or HBA as reactive diluents in the crosslinkable polymer. In some exemplary manufacturing methods, no phase separation occurred upon curing and the cured polymer material was transparent. Formulations based on these crosslinkable polymers are highly suitable for high precision (very low shrinkage) manufacturing of directly molded parts, such as in haptics and optics or any of the accommodating intraocular lenses described herein or incorporated by reference herein.

A further typical advantage of incorporating one or more hydrophilic monomers (e.g., HEMA, HBA) as reactive diluents into a polymeric material is the reduction of water-induced haze or glistening (i.e., water blisters in the material).

5A and 5B show the polymerization of exemplary hydrophilic materials, HEMA is shown in FIG. 5A and HBA in FIG. 5B.

glue

One aspect of the present disclosure describes an adhesive that can be used to bond a first and a second polymer, optionally a first and a second polymer of an intraocular lens, together. Although the present disclosure describes adhesives and polymers for use in ophthalmic applications, it is not intended to be so limited. The materials described herein can be used in other suitable applications. The exemplary polymer materials above (e.g., Example 1, Example 2, and Table 1) are merely examples of polymeric formulations for the first and second components to be bonded together. The adhesives described herein will be described in relation to the polymers described herein, but the concepts herein can be applied to other polymeric materials and other adhesives. The examples shown herein are merely exemplary, and the present disclosure is not intended to be limited to the specific adhesives or the specific polymers herein.

During the manufacture of some ophthalmic devices, two or more polymeric objects are adhered or glued together. The adhesion should be strong enough so that the two or more objects remain adhered to each other during use and during the implantation procedure. For example, the adhesion should be maintained even if the device needs to be reconfigured or deformed when worn and/or delivered into the eye. Furthermore, the presence of the adhesive should not cause the optical clarity of the device to be reduced to an unacceptable level, such as at or near the adhesive. The adhesive and polymer combination herein not only maintains an acceptable level of optical clarity, but also improves or maintains the mechanical integrity of the adhesive/polymer bond.

One aspect of the present disclosure is an adhesive having a first component that is the same or substantially the same material or has substantially similar properties as a first and second polymeric object being adhered to one another. The first and second objects may alternatively have different formulations. As used herein, an adhesive is used to adhere a "first object" to a "second object."

In some embodiments, the first and second objects are first cured and then adhered to one another using the adhesion techniques herein.

In some embodiments, the adhesive comprises a first and second main component and a curable additive (e.g., photoinitiator). In a purely exemplary embodiment, including an exemplary manufacturing method, the first main component (e.g., about 50-75%) is a crosslinkable polymer ("CLP"; the above discussion of crosslinkable polymers is incorporated into this aspect of the disclosure) that has the same or similar composition or substantially similar properties as the first and second objects. Because the CLP has not yet crosslinked, it behaves as a flowable, soluble, thermoplastic material rather than a thermosetting material. The CLP then combines with the second main component, a reactive acrylic monomer diluent (e.g., ADMA, etc., as shown in FIG. 16, e.g., about 20-50%), and the remaining component is a photoinitiator at about 2% to cure the adhesive. At the bond line between the first and second objects, the CLP is too large/bulky to migrate into either object, while the reactive acrylic monomer diluent and photoinitiator can migrate/diffuse across the bond line into both cured polymeric objects. Depending on the time, temperature, and thickness of the bond line, the reactive acrylic monomer diluent and initiator will diffuse to a certain degree (controllable) and then cure (e.g., with UV light) to create an interpenetrating network of reactive acrylic monomer diluent (e.g., ADMA) in the first and second objects, as well as a now crosslinked polymer (that is the same or similar, or has similar properties as the first and second objects) that also contains a network of interpenetrating reactive acrylic monomer diluent. If the degree of diffusion is such that the concentration of reactive acrylic monomer diluent is essentially the same across the bond line and within the bond line, then the properties of the material will be substantially the same across the regions.

In some embodiments, the first major component (optionally having the same or similar composition as the first and/or second objects) is about 55% to about 80% (e.g., about 55% to about 75%) of the adhesive, and in some embodiments, the second major component (the reactive acrylic monomer diluent) is about 18% to about 43% (e.g., about 23% to about 43%) of the adhesive.

The adhesives herein provide several mechanical advantages. In general, the bond strength improves over time, which increases the useful life of the device. When using substantially the same materials, or materials with substantially similar properties, an interpenetrating network of materials is formed between the polymer and the adhesive, where the resulting adhesive material is substantially the same throughout. Furthermore, the mechanical and thermal properties of the materials can also be substantially the same. For example, the elastic modulus of the polymer and the adhesive can be designed to be the same or substantially the same. Furthermore, the surface energy can be substantially the same, which helps to retain ambient water from the adhesive and prevents it from migrating into the device and forming water droplets.

Furthermore, when using a first component of the adhesive that is the same or substantially the same as the material of the first object, crosslinking can be better controlled during manufacturing, which leads to less shrinkage when the adhesive cures. While shrinkage always occurs when monomers cure (typically about 10% by volume for most acrylic monomers), crosslinking of CLP occurs with almost no shrinkage, since it can essentially be considered the last about 1% of all pre-cured materials, so the more CLP used in the adhesive formulation, the less shrinkage the formulation will exhibit when cured. Furthermore, when ADMA, for example, diffuses into the bonded acrylic, an associated swelling follows, which may offset some or all of the shrinkage caused by curing.

In one aspect of the present disclosure, the term "substantially the same" is intended to include compositions that contain approximately the same amounts of the same components, or similar components, or that have properties that are substantially the same. In some embodiments, the term substantially the same can refer to compositions that contain the same components, where the percentage of each component, either by weight or volume, is within 1-50% of the components of the compared composition. In other embodiments, substantially the same may be used to refer to compositions that have substantially the same physical properties (e.g., viscosity, refractive index, structure, etc.).

Furthermore, there are optical advantages in using adhesive materials that include a first component that is the same or substantially the same as the polymeric object material. As indicated above, the surface energy may be substantially the same and there are substantially no hydrophobic sites. The substantially same surface energy prevents water droplets from forming, which prevents the optical transparency from decreasing. Furthermore, by using substantially the same materials, the refractive index of the adhesive and the bonded polymer can be made substantially the same. Although the difference in refractive index between the adhesive and the polymer does not cause significant optical disturbances, making the materials with substantially the same refractive index can reduce the possibility of such disturbances.

The crosslinkable polymer of the adhesive does not have to have the same formulation (same monomers and same percentages) or even the same monomers as the polymer formulation of the first and/or second polymeric objects to be bonded together. It is advantageous for the crosslinkable polymer formulation to have similar properties to the formulation of the first and/or second polymeric objects described above, but in other embodiments they are very different. By way of example only, formulation #4 of the table has been used as the crosslinkable polymer in an adhesive formulation and has been used to bond polymeric objects having a formulation as shown in any of formulations #1-#3 of Table 1. In this example, the crosslinkable polymer of the adhesive and the polymer formulation of the first and second objects both contain the same three monomers, but in different percentages. This is an example of having substantially the same or substantially similar properties. The bond strength in this example was very strong. In some embodiments, the crosslinkable polymer of the adhesive and the polymer formulation of the first and second objects may be the same.

Any intraocular lens that includes first and second members that are bonded together can be bonded together using the concepts herein.

In some embodiments, the adhesive is formed according to the method shown in Figure 16 above to form a crosslinkable polymer, i.e., a prepolymer is used to form a crosslinked polymer to create a crosslinkable polymer that can be cured with the first and second objects when mixed with a reactive diluent (e.g., ADMA).

The disclosure herein also describes exemplary fluids that can be used in the intraocular lens. In some embodiments, the fluid is a silicone oil, and in some embodiments, the intraocular lens is an accommodating intraocular lens.

The ophthalmic device may contain one or more silicone oils. Silicone oil may be used in accommodative intraocular lenses that use fluid movement to change the refractive power of the IOL. Silicone oil may also be used in non-accommodative intraocular lenses. When silicone oil is used in accommodative IOLs that include bulk materials such as polymeric materials, some of the oil components can pass into the bulk material, causing the bulk material to swell. Thus, the selected silicone oil or oils prevent undesired swelling of the bulk polymer. Exemplary polymeric materials that can be used for the bulk material of the IOL can be found herein.

The amount of silicone oil diffusing through the polymer can be reduced by selecting a silicone oil with a narrow molecular weight distribution, especially one that has had low molecular weight silicone oil molecules removed. A series of stripping methods can be used to remove the low molecular weight components in the silicone oil. In general, low molecular weight components will diffuse faster than high molecular weight components. However, high molecular weight components contribute to increased viscosity, which requires more force to pump the fluid through the IOL. Therefore, silicone oils with a narrow molecular weight distribution are preferred. The fluid placed in the ophthalmic device is not limited to silicone oil, and can be, for example, saline.

One property of silicone oil that helps ensure sufficient response and prevents undesired swelling is the polydispersity index ("PDI") of the silicone oil to be used in the IOL. PDI is generally a measure of the distribution of molecular weights of a given sample. A relatively low PDI indicates a relatively narrow range of molecular weights. The silicone oils described herein have a PDI of less than about 1.5, more specifically less than or equal to about 1.3. In another example, the PDI of the silicone oil is less than about 1.2.

A second property of the silicone oil that helps ensure adequate response and prevents unwanted swelling is the average molecular weight of the silicone oil. If a high concentration of relatively low molecular weight components is present in the silicone oil, more of the low molecular weight components will pass into the bulk material of the IOL, causing swelling of the bulk material. To prevent unwanted swelling, the concentration of the relatively low molecular weight components should be minimized. By reducing the concentration of the relatively low molecular weight components and maintaining a high concentration of relatively high molecular weight components, less low molecular weight components will pass into the bulk polymer material, reducing the amount of swelling that occurs in the bulk material.

The PDI of silicone oil and the average molecular weight of the oil are related.By lowering the PDI of silicone oil, while providing silicone oil with a high concentration of relatively high molecular weight components and a low concentration of low molecular weight components, the response of IOL is maintained (by providing silicone oil with appropriate viscosity) and undesirable swelling is avoided.Furthermore, providing silicone oil with low PDI and very low concentration of low molecular weight components means that silicone oil has molecular weight of the minimum necessary size to prevent polymer swelling.

In some embodiments, silicone oils are provided with an average molecular weight of about 4500 to about 6500 Daltons, or an average molecular weight of about 5000 to about 6500 Daltons. Silicone oils with molecular weights in this range are large enough to substantially prevent swelling of bulk polymeric materials. This is preferable to alternative methods that use higher molecular weight silicone oils that are essentially less low molecular weight because almost all of the molecules that make them up are large. Thus, high molecular weight silicone oils can have high viscosity, which can shorten the response time of accommodative IOLs.

Silicone oils described herein have a very low concentration of relatively low molecular weight components.Very low molecular weight components are present in an amount of less than about 200 ppm, and in some embodiments less than about 100 ppm, of each component.In some specific embodiments, very low molecular weight components are present in an amount of less than about 50 ppm.

Relatively low molecular weight components include those below about 1000 Daltons. For example, in some embodiments, the concentration of components below about 1000 Daltons is below about 50 ppm.

In one particular embodiment, a silicone oil is provided in which no more than 20% of the total silicone is made up of components less than about 4000 Daltons; no more than 10% by weight of the total polymer fluid is made up of components less than 3000 Daltons; and no more than 50 ppm is made up of any component less than 1000 Daltons.

Estimated molecular weights and polydispersities given herein are relative to polystyrene molecular weight standards.

Silicone oils generally need to be designed in such a way as to prevent adverse interactions with the surrounding bulk IOL material in some IOLs, such as swelling, fogging, dissolving, or reacting with the material (e.g., polyacrylates). The solubility of the silicone oil in the bulk material is determined by the chemical structure and molecular weight distribution of the silicone oil. Other parameters that affect this interaction are the composition and properties of the bulk material, such as homogeneity, chemical structure, hydrophobicity, elastic modulus, and crosslink density.

It is also generally necessary that the viscosity of the silicone oil be defined and minimized, since in embodiments where the fluid-driven accommodative IOL is dynamically actuated, the IOL must have adequate response time. In some embodiments, the viscosity of the silicone oil is 2400 cP or less.

In some embodiments, the silicone oil is made from a cyclotrisiloxane that contains a ratio of two dimethylsiloxane units to one diphenylsiloxane unit, hi some embodiments, the oil is at least 95% (e.g., 100%) a single cyclotrisiloxane that contains a ratio of two dimethylsiloxane units to one diphenylsiloxane unit.

In some embodiments, the oil is a copolymer of diphenylsiloxane and dimethylsiloxane comprising about 20% diphenylsiloxane and about 80% dimethylsiloxane.

In some embodiments, the silicone oil may be a single component of diphenylsiloxane (e.g., approximately 100%). In other embodiments, the percentage of diphenylsiloxane is approximately 95% or greater. In these embodiments, the refractive index of the silicone oil is approximately 1.5180, which is an example of a range of 1.50-1.53. In some embodiments, a silicone oil that is approximately 100% diphenylsiloxane may be used in an accommodating intraocular lens having a formulation such as #1-#3 in the table above. In these embodiments, the fluid and polymer are index matched to approximately 1.518.

In some embodiments, the average molecular weight of the diphenylsiloxane polymer compound is from about 4500 to about 6500 Daltons.

In some IOLs, it may be desirable to avoid creating an optical interface between the bulk material of the IOL and the silicone oil within the IOL. This can be done by index matching the silicone oil to the bulk material of the IOL, which in some embodiments is a polymeric material. As used herein, "index matching" refers to minimizing the optical interface between the first and second medium. For example, index matching a silicone oil and a polymeric material refers to attempting to eliminate the optical interface between them, and "substantially the same" refers to refractive indices that are intended to be as close as possible, even if they are slightly different, to minimize the difference in refractive index.

In some embodiments where the silicone oil is index matched to the bulk polymer material, the refractive index of the silicone oil is from about 1.47 to about 1.55, and in some embodiments, from about 1.50 to about 1.53.

In some embodiments, the silicone oil should be capable of being filtered through a filter of about 0.7 microns. In some embodiments, the percent of volatiles is less than about 0.2%. In some embodiments, the silicone oil has a wavelength dispersion of about 0.035 or less refractive index units at 35°C within the visible range of 400 nm to 750 nm. In some embodiments, the silicone oil components are completely miscible with each other with no signs of phase separation (i.e., cloudiness or turbidity). In some embodiments, the silicone oil has a transmission of greater than 85% for a fluid sample about 1 cm thick within the range of 400 nm to 1100 nm.

Additionally, the silicone oil should be clear, colorless, contain less than about 10 ppm of heavy metals and other insoluble inorganic impurities, and be substantially free of silanols.

Silicone Oil Synthesis

The molecular weight, polydispersity, and sometimes refractive index of silicone oil can be controlled by the method of synthesis and purification of silicone oil.The viscosity of oil is related to the molecular weight of oil, the polydispersity of oil, and the structure of bulk polymer, all of which are affected by the synthesis and purification of polymer.However, the target viscosity cannot be arbitrarily selected, independent of the target molecular weight, polydispersity, composition, and structure of silicone oil.A general class of polymer synthesis reactions known as "living polymerization reactions" can provide the degree of control required to help meet some of the design requirements of silicone oil.

The term "living polymerization" refers to a polymerization reaction that does not undergo a large number of chain termination or chain transfer side reactions. The absence of side reactions allows living polymerization to be used to synthesize a variety of materials that are otherwise difficult to prepare. This class of polymerization reactions can be used to prepare polymers with a variety of 1) structures--including linear, "star" and "comb" polymers; 2) compositions--homopolymers, random copolymers, block copolymers and graft copolymers; and 3) functionalized polymers--mono- and di-end functional polymers as well as side chain functional polymers. This class of polymerization reactions can be used to prepare polymers at a variety of molecular weights, often with narrow molecular weight distributions. As a result, living polymerization is often employed when a polymer with a specific structure and composition is required. For example, a polymer with a broad molecular weight distribution can be considered a mixture of many compounds, and the properties of the material are some function of that distribution. However, a polymer with a narrow molecular weight distribution, such as can be obtained from living polymerization, can be considered a "pure" sample with better defined properties.

Anionic and cationic living polymerizations have been described in the art. More recently, radical living polymerizations have been developed. In one example of anionic synthesis route, the use of alkyllithium compounds in the ring-opening polymerization of cyclotrisiloxanes is considered to be a "living" polymerization, allowing the degree of control required to make the silicone oils described above. By varying the ratio of phenyl-containing cyclotrisiloxanes to methyl-only containing cyclotrisiloxanes (i.e., preparing random block copolymers), the refractive index of silicone oils can be changed between the refractive indexes of both pure homopolymers alone (i.e., between pure diphenylpolysiloxanes and pure dimethylpolysiloxanes).

As another example, the refractive index of the silicone oil composition can be varied by varying the ratio of tetramethyl-diphenyl-cyclotrisiloxane to hexamethylcyclotrisiloxane to achieve a range of refractive indices from about 1.40 to about 1.54, including refractive indices from about 1.47 to 1.49.

As mentioned above, living polymerization also offers the advantage of being able to prepare polymer products of targeted molecular weights. This can be achieved by varying the monomer to initiator ratio during the polymerization reaction, a process that can be applied to prepare specific formula weight silicone oils.

The narrow molecular weight product feature is also an advantage that can be realized in the preparation of silicone oils because less low molecular weight oligomers are produced during the polymerization reaction. The smaller amount of low molecular weight material produced minimizes the amount of subsequent purification required to remove the low molecular weight material from the higher molecular weight product. For example, if only a small amount of low molecular weight oligomers are produced during the polymerization reaction, then supercritical CO₂When extraction (described below) is used to purify synthetic silicone oils, it is easier to extract the low molecular weight materials, resulting in higher yields of the desired product.

Although the viscosity of a polymer is not directly related to the method of preparing the polymer, living polymerization can also be used to indirectly modify this characteristic of the product polymer.Living polymerization can be used to create polymer structures that are difficult to achieve using other synthetic methods.For example, "comb" polymers, "star" polymers, and other branched structures can be prepared, which may have very similar chemical compositions to "linear" polymers, but may have different physical properties (e.g., viscosity) due to the different physical shapes that these structures have.Preparing highly branched silicone oils can result in products with significantly lower viscosities than silicone oils with the same molecular weight but linear structure.

Silicone oils can also be prepared using other synthetic methods, such as the base-catalyzed ring-opening of cyclotrisiloxanes and the condensation of dialkyldichlorosilanes with water. These synthetic methods can also produce silicone oils with many of the above properties, but may require more purification effort.

Silicone oil purification

Silicone oils can be purified in a variety of ways. The silicone oil obtained after the polymerization reaction as discussed above may contain silicone oil polymer variants with various molecular weights. Low molecular weight silicone oils can cause undesirable swelling of the bulk polymeric material and should be minimized. Wiped film evaporation can be used to remove low molecular weight compounds with high boiling points. However, the silicone oil product may discolor due to excessive heating when using wiped film evaporation.

Supercritical CO₂Extraction is one exemplary purification method that can be used to selectively remove fractions of silicone oil based on molecular weight and based on chemical affinity. Supercritical CO extraction to purify silicone oil to produce silicone vitreoretinal tamponade₂Extraction is described in U.S. Patent No. 7,276,619, the entire disclosure of which is incorporated herein by reference. These oils are not used in IOLs, particularly in fluid-driven accommodative IOLs. Pressure, temperature, extraction rate conditions, and the use of coeluting solvents such as acetone can be varied to obtain fractions with narrow molecular weight distributions (i.e., low PDI). Mixtures can be separated in such a way that very low and very high molecular weight fractions are removed from the sample to obtain the desired molecular weight. Since supercritical extraction conditions can be varied to obtain separations based on chemical affinity, this purification method can also be used to obtain the desired refractive index. Thus, supercritical CO₂Extraction can be used, for example, to produce a silicone oil that has substantially the same refractive index as the bulk polymer intended for use in an intraocular lens (eg, in a fluid-driven accommodating intraocular lens).

Tables 2 (Table 4) to 4 (Table 6) show exemplary supercritical CO₂Data from an extract is shown.

<tables><img file="JP2024166312A_D0004.tif" /></tables>

<tables><img file="JP2024166312A_D0005.tif" /></tables>

<tables><img file="JP2024166312A_D0006.tif" /></tables>

Similarly, preparative-scale size-exclusion chromatography is an alternative method for fractionating polymer samples into molecular weight components. Fractional precipitation of silicone oil may also be used to separate components of the product polymer.

Removal of silicone oil components that dissolve into the bulk IOL material over time (e.g., during storage) may be accomplished by exposing the silicone oil to a bulk amount of the IOL material, or other material selected for that purpose. When stored with the appropriate materials, components of the silicone oil that dissolve into the bulk IOL polymer material can be removed by adjusting the silicone oil to polymer sorbent ratio so that only sufficiently low levels of those materials remain in the oil.

An important aspect of the fractionated oils herein is their very low polydispersity ("PDI") (e.g., less than 1.5, less than 1.3, or even less than 1.2) that could not be obtained by other known polymerization methods. One way to obtain desired properties that were previously unattainable is to fractionate the oil after synthesis to remove the very low molecular weight fraction (and sometimes also the very high molecular weight fraction). The very low PDI provides the advantage of matching the material properties to the functional properties; in particular, high molecular weight (hence low swelling and refractive power stability) and low viscosity (hence fast response time of accommodation and disaccommodation). A further benefit of some embodiments herein, including blended high and low refractive index oil components, such as those in Tables 5 and 6 below (e.g., blended dimethylsiloxane vs. diphenylsiloxane), is that despite the high molecular weight of the fractionated oils, the blended index-matched system (index-matched to the polymeric material of the lens) does not actually increase viscosity significantly due to the change in blend ratio coupled with the intrinsic viscosity change as a function of component content (e.g., oil components are dimethylsiloxane and diphenylsiloxane).

Tables 6 and 7 show examples of unfractionated and fractionated blends (high and low RI) of exemplary silicone oils, respectively. The exemplary blend oils in Tables 5 and 6 have viscosities of less than 1000 cPs and blended refractive indices of 1.47 to 1.50.

<tables><img file="JP2024166312A_D0007.tif" /></tables>

<tables><img file="JP2024166312A_D0008.tif" /></tables>

One exemplary method of making oils with very low PDI is by using fractionation methods that are consistent, reliable, reproducible, scalable, highly accurate, etc. Fractionation methods allow for property matching of silicone fluids to acrylic lens materials that cannot be achieved by other methods, thereby minimizing optical power shifts due to swelling, while maintaining a desirable low viscosity fluid that allows for acceptably fast response times, both of which are described herein.

An exemplary method is hot isopropyl alcohol/water fractionation: the only reagents used are isopropyl alcohol and water, which can be evaporated off from the oil.

In exemplary embodiments, the oil comprises a blend of dimethylsiloxane and diphenylsiloxane, examples of which are set forth herein in the Tables, etc. In some embodiments, the oil comprises a copolymer of dimethylsiloxane and diphenylsiloxane, and in some embodiments, the ratio of the two may vary from 1:1 to 3:1.

Table 7 lists exemplary silicone oils, including average molecular weight, polydispersity, and predicted dispersion. The polydispersity of these examples are all less than 1.3, including the example below 1.5.

<tables><img file="JP2024166312A_D0009.tif" /></tables>

Table 8 lists exemplary silicone oils, including the average molecular weight, polydispersity, and refractive power variations. The polydispersity of these examples is all less than 1.3, and this is an example below 1.5.

<tables><img file="JP2024166312A_D0010.tif" /></tables>

In some embodiments, the average molecular weight of the oil is from about 4500 Da to about 6500 Da, and in some embodiments, from 5000 Da to 6000 Da, such as from about 5200 Da to 5800 Da. In some embodiments, the viscosity is less than 2400 cPs.

Although silicone oils used in accommodative IOLs are primarily described herein, it is possible to use any of the silicone oils in non-accommodative IOLs.For example, non-accommodative IOLs may have a relatively hard outer polymer shell surrounding a silicone oil core.The swelling of bulk polymeric materials must still be taken into consideration, and therefore the methods of making the desired silicone oils described herein can be utilized.

In some embodiments of US2013/0131794, the accommodating intraocular lens includes an optic that includes an anterior lens element and a posterior lens element that define an optic fluid chamber. In some embodiments, the fluid can be substantially index matched to the material of the anterior and posterior elements (making the optic essentially behave like a lens), while in some embodiments the fluid has a different index of refraction than one or both of the anterior and posterior lens elements. By placing a fluid in the optic chamber with a different index of refraction, two additional optical interfaces can be created within the optic (anterior lens element/fluid interface, and a fluid/posterior lens element interface). By providing additional optical interfaces, further control can be exerted over the optical power of the IOL throughout the process of accommodation.

The following are examples of the embodiments of the present invention.

[Embodiment 1]

An intraocular lens comprising a polymeric material comprising butyl acrylate present in an amount between 2% and 20%, trifluoroethyl methacrylate present in an amount between 10% and 35%, and phenylethyl acrylate present in an amount between 50% and 80%.

[Embodiment 2]

2. The intraocular lens according to embodiment 1, wherein the polymer material has a refractive index of 1.48 to 1.53.

[Embodiment 3]

The intraocular lens according to embodiment 2, wherein the refractive index of the polymer material is 1.50 to 1.53.

[Embodiment 4]

2. The intraocular lens of embodiment 1, wherein the polymeric material defines a fluid channel, and the intraocular lens further comprises silicone oil in the fluid channel.

[Embodiment 5]

5. The intraocular lens of embodiment 4, wherein the silicone oil is index matched to the polymer material.

[Embodiment 6]

5. The intraocular lens of embodiment 4, wherein the silicone oil has a polydispersity of less than 1.2.

[Embodiment 7]

1. A polymeric material for an ophthalmic device comprising: an alkyl acrylate present in an amount between 3% and 20%; a fluoroacrylate present in an amount between 10% and 35%; and a phenyl acrylate present in an amount between 50% and 80%.

[Embodiment 8]

An accommodating intraocular lens comprising: an optic portion adapted to refract light onto the retina, the optic portion comprising a polymeric material; and a silicone oil disposed within the optic portion, the silicone oil having a polydispersity index of less than about 1.2.

[Embodiment 9]

The accommodating intraocular lens according to embodiment 8, wherein the average molecular weight of the silicone oil is 4,500 to 6,500.

[Embodiment 10]

An accommodating intraocular lens as described in embodiment 8, having a viscosity of 2400 cP or less.

[Embodiment 11]

The accommodating intraocular lens of embodiment 8, wherein the silicone oil comprises diphenylsiloxane units.

[Embodiment 12]

The accommodating intraocular lens of embodiment 8, wherein the silicone oil is made of cyclotrisiloxane containing a ratio of two dimethylsiloxane units to one diphenylsiloxane unit.

[Embodiment 13]

The accommodating intraocular lens according to embodiment 8, wherein the refractive index of the silicone oil is 1.47 to 1.53, optionally 1.50 to 1.53.

[Embodiment 14]

An adhesive for an accommodating intraocular lens, the adhesive comprising a first component having the same or substantially similar properties as a polymeric material of a first object of the accommodating intraocular lens.

[Embodiment 15]

15. The adhesive of embodiment 14, comprising a first component that is the same as the polymeric material of the first object of the intraocular lens.

[Embodiment 16]

16. The adhesive of embodiment 15, comprising a first component comprising a monomer present in a polymeric material.

[Embodiment 17]

15. The adhesive of embodiment 14 comprising a second main component which is a reactive acrylic diluent.

[Embodiment 18]

15. The adhesive of embodiment 14, comprising a first component that is substantially similar, but not the same, to the polymeric material of the first object of the accommodating intraocular lens.

[Embodiment 19]

1. A method of manufacturing an accommodating intraocular lens, comprising: curing first and second components of the accommodating intraocular lens; and applying an adhesive between the first and second components, the adhesive comprising a first component having the same, substantially the same, or substantially similar properties as at least one of the first and second components, and further comprising a second main component that is a reactive acrylic diluent.

[Embodiment 20]

A method for producing a polymeric component of an intraocular lens comprising a plurality of monomers, the method comprising the steps of: forming a polymeric prepolymer comprising the plurality of monomers; and curing the prepolymer to form the polymeric component.

[Embodiment 21]

21. The method of embodiment 20, wherein forming the prepolymer comprises combining a plurality of monomers with a monomer that includes a hydroxy moiety.

[Embodiment 22]

22. The method of embodiment 21, further comprising forming a crosslinkable polymer from the prepolymer, wherein forming the crosslinkable polymer comprises converting hydroxyl moieties to methacrylate moieties.

The present disclosure also includes the following aspects.

[Aspect 1] A method for manufacturing at least one of a support portion and an optical portion of an intraocular lens, the method comprising: combining a plurality of monomers with additional monomers comprising hydroxyl moieties, the plurality of monomers comprising butyl acrylate, trifluoroethyl methacrylate, and phenylethyl acrylate; and curing the plurality of monomers and the additional monomers to form at least one of the support portion and the optical portion of the intraocular lens, the curing converting the hydroxyl moieties to crosslinkable methacrylates.

[Aspect 2] The method of aspect 1, wherein the additional monomer containing a hydroxyl moiety is hydroxyethyl methacrylate (HEMA).

[Aspect 3] The method of aspect 1, wherein the additional monomer containing a hydroxyl moiety is hydroxyethyl acrylate (HEA).

[Aspect 4] The method of aspect 1, wherein the additional monomer containing a hydroxyl moiety is hydroxybutyl acrylate (HBA).

[Aspect 5] The method of aspect 1, wherein the additional monomer containing a hydroxyl moiety is added to reduce haze or glistening due to water.

[Embodiment 6] The method of embodiment 1, wherein curing comprises UV curing in the presence of a photoinitiator.

[Aspect 7] A method for manufacturing an intraocular lens, the method comprising: forming a first body and a second body of the intraocular lens; applying an adhesive between the first body and the second body, the adhesive comprising a first main component having the same, substantially the same, or substantially similar properties as a polymeric material constituting the first body or the second body, the first main component being present in the adhesive in an amount between 55% and 80%, and a second main component; and bonding the first body to the second body by curing the adhesive, the adhesive creating an interpenetrating network of reactive acrylic diluent within the first body and the second body upon curing.

[Aspect 8] The method of aspect 7, wherein applying adhesive further includes applying the adhesive along a circular raised periphery of a posterior element of the intraocular lens, the adhesive being used to adhere the posterior element to an anterior element of the intraocular lens.

[Aspect 9] The method of aspect 7, wherein the first main component includes trifluoroethyl methacrylate, at least one of butyl acrylate and n-butyl methacrylate, and at least one of phenylethyl acrylate and phenylethyl methacrylate.

[Aspect 10] The method of aspect 9, wherein the first main component is a crosslinkable polymer that has not yet been crosslinked, and the crosslinkable polymer is bulky and cannot migrate into either the first body or the second body.

[Aspect 11] The method of aspect 7, wherein the second main component is a reactive acrylic monomer diluent.

[Aspect 12] The method of aspect 11, wherein the reactive acrylic monomer diluent is 1-adamantyl methacrylate (ADMA).

[Embodiment 13] The method of embodiment 7, wherein the second main component is present in the adhesive in an amount between 18% and 43%.

[Embodiment 14] The method of embodiment 7, wherein the adhesive further comprises a photoinitiator.

[Embodiment 15] The method of embodiment 14, wherein the photoinitiator is present in the adhesive in an amount of about 2% of the adhesive formulation.

[Example 16] The method of Example 7, wherein the adhesive is cured using UV light.

[Embodiment 17] A method for purifying a silicone oil for use in an accommodative intraocular lens, the method comprising: fractionating a silicone oil using a fractionation process including heated isopropyl alcohol and water as reagents; and evaporating the isopropyl alcohol and water from the silicone oil.

[Embodiment 18] The method of embodiment 17, wherein the fractionated silicone oil obtained from the fractionation process has a polydispersity index (PDI) of less than 1.2.

[Aspect 19] The method described in aspect 17, wherein the average molecular weight of the silicone oil is between 4500 and 6500.

[Aspect 20] The method described in aspect 17, wherein the silicone oil contains dimethylsiloxane and diphenylsiloxane, and the ratio of dimethylsiloxane to diphenylsiloxane is between 1:1 and 3:1.

10 Accommodative intraocular lens

12 Optical section

14 Support

18 Front Element

20 Rear element

twenty two Support Fluid Chamber

twenty four Optical Fluid Chamber

26 Opening

28 Peripheral Surface

29 Buttress section

32 Flow Path

42 Outer part of the support