Intraocular lens materials and components

Abstract

With respect to intraocular lens materials and components, the polymer and / or fluid are adapted such that fluid swelling into the polymer material is minimized or even prevented, and a fluid having a refractive index as close as possible to the refractive index of the bulk polymer material is provided. [Solution] A material for an intraocular lens and a method for manufacturing an intraocular lens, comprising a polymer material for an intraocular lens, a fluid for an intraocular lens, and an adhesive for an intraocular lens. The intraocular lens may include an optical portion and peripheral regions that are in fluid communication.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 62 / 173,877, filed Jun. 10, 2015, which is incorporated herein by reference. This application also claims the benefit of U.S. Provisional Application No. 62 / 321,704, filed Apr. 12, 2016, which is incorporated herein by reference.

[0002] This application relates to the following applications and patents: U.S. Patent No. 8,900,298, issued Dec. 2, 2004; U.S. Patent Publication No. 2013 / 0131794, published May 23, 2013; U.S. Patent No. 8,158,712, issued Apr. 17, 2012, each of which is incorporated herein by reference. Incorporation by Reference

[0003] All publications and patent applications mentioned in this specification are incorporated herein by reference as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

Background Art

[0004] Presbyopia is a condition in which the eye loses its ability to focus on nearby objects. This is part of what naturally occurs with aging and often becomes noticeable in people in their mid - 40s and may continue to worsen until about age 65. In order for the eye to clearly see nearby objects, it is necessary to increase the refractive index of the eye lens or make its shape more convex to improve focusing on nearby objects.

[0005] Cataracts are the leading cause of blindness worldwide and the most common eye disease, resulting in over 8 million consultations per year. When cataract impairment affects or alters an individual's daily activities, cataract surgery with intraocular lens (IOL) implantation is the preferred way to treat the associated visual limitations. In the United States, approximately 2.5 million cataract surgeries are performed annually, making it the most common surgery for Americans over 65. With about 97 percent of cataract patients receiving IOL implantation each year, the annual cost of cataract surgery and related care in the United States exceeds $4 billion.

[0006] Cataracts are defined as clouding of the lens of a patient's eye, whether localized or diffuse, overall loss of clarity. However, for a cataract to have clinical significance, it must be caused by a significant decrease in visual acuity or functional impairment. Cataracts can result from aging, or from genetic factors, trauma, inflammation, metabolic or nutritional disorders, or radiation. Age-related cataracts are the most common.

[0007] In cataract treatment, the surgeon removes the lens matrix from the lens capsule and replaces it with an intraocular lens ("IOL") implant. A typical IOL achieves a selected focal length, allowing the patient to have fairly good distance vision. However, after cataract surgery, patients typically require reading glasses. This is explained by the imaging characteristics of the human eye, which are facilitated by several optical interfaces.

[0008] In addition to age-related declines in accommodative ability, such declines have also affected IOLs used to treat cataracts. While research on accommodative IOLs has yielded some results, the relative complexity and limited effectiveness of the methods and devices developed so far have hindered the widespread commercialization of such devices.

[0009] Some intraocular lenses include an optical component, one or more of which are polymers. It is desirable that the polymer has properties that allow the intraocular lens to deform into a delivery shape that can be implanted in the eye, and that it can return to its pre-implantation shape after implantation. Furthermore, it is desirable that the polymer composition has a sufficiently high refractive index.

[0010] Some intraocular lenses described herein contain fluids such as silicone fluids. 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 fluids such as silicone oils are used in intraocular lenses, the fluid tends to swell into the bulk polymer material of the intraocular lens over time. This can reduce the amount of silicone oil available to drive refractive power changes in the IOL. Therefore, it is 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 is desirable to adapt the polymer and / or fluid so that the swelling of the fluid into the polymer material is minimized or even prevented.

[0011] In IOLs containing different types of materials (e.g., cured polymers and silicone oils), it may be desirable to substantially match the refractive index of the different types of materials (i.e., have the same or substantially the same refractive index). Therefore, it may also be beneficial to provide a fluid having a refractive index as close as possible to that of the bulk polymer material. [Prior art documents] [Patent Documents]

[0012] [Patent Document 1] U.S. Patent No. 7,276,619 [Overview of the project] [Means for solving the problem]

[0013] One aspect of the present disclosure is an intraocular lens comprising a polymer material containing butyl acrylate in an amount of 2% to 20%, trifluoroethyl methacrylate in an amount of 10% to 35%, and phenylethyl acrylate in an amount of 50% to 80%.

[0014] In some embodiments, the refractive index of the polymer material is 1.48 to 1.53. In some embodiments, the refractive index of the polymer material is 1.50 to 1.53.

[0015] In some embodiments, the polymer material defines fluid channels, and the intraocular lens further contains silicone oil within the fluid channels. In some embodiments, the silicone oil is refractive index matched with the polymer material. In some embodiments, the polydispersity of the silicone oil is less than 1.2.

[0016] One aspect of the present disclosure is a polymer material for ophthalmic devices comprising an alkyl acrylate present in an amount of 3% to 20%, a fluoroacrylate present in an amount of 10% to 35%, and a phenyl acrylate present in an amount of 50% to 80%.

[0017] One aspect of the present disclosure is an accommodative intraocular lens comprising: an optical portion comprising a polymer 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 optical portion.

[0018] In some embodiments, the average molecular weight of the silicone oil is 4500 to 6500.

[0019] In some embodiments, the viscosity is 2400 cP or less.

[0020] In some embodiments, the silicone oil contains diphenylsiloxane units.

[0021] In some embodiments, the silicone oil is made from a cyclotrisiloxane containing a ratio of two dimethylsiloxane units to one diphenylsiloxane unit.

[0022] In some embodiments, the refractive index of the silicone oil is 1.47 to 1.53, optionally 1.50 to 1.53.

[0023] One aspect of the present disclosure is an adhesive for an accommodative intraocular lens, the adhesive comprising a first component having the same or substantially similar properties as the polymeric material of the first object of the accommodative intraocular lens.

[0024] 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. In some embodiments, the adhesive comprises a first component that comprises monomers present in the polymeric material.

[0025] In some embodiments, the adhesive comprises a second main component that is a reactive acrylic diluent.

[0026] In some embodiments, the adhesive comprises a first component that is not the same as the polymeric material of the first object of the accommodative intraocular lens but is substantially similar. material and includes a first component that is not the same as the polymeric material of the first object of the accommodative intraocular lens but is substantially similar.

[0027] [[ID=2*]] One aspect of the present disclosure is a method of manufacturing an accommodative intraocular lens, the method comprising curing the first and second members of the accommodative intraocular lens; and applying an adhesive between the first member and the second member, 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 members and further comprising a second main component that is a reactive acrylic diluent.

[0028] One aspect of the present disclosure is a method of manufacturing a polymeric component of an intraocular lens comprising a plurality of monomers, the method comprising forming a prepolymer of the polymer comprising the plurality of monomers; and curing the prepolymer to form the polymeric component.

[0029] In some embodiments, the step of forming a prepolymer includes a step of combining a plurality of monomers with a monomer containing a hydroxyl moiety. The method may further include a step of making a crosslinkable polymer from the prepolymer, the step of making a crosslinkable polymer includes a step of changing the hydroxyl moiety to a methacrylate moiety. [Brief explanation of the drawing]

[0030] [Figure 1A] This is a diagram illustrating an exemplary accommodative intraocular lens. [Figure 1B] This is a diagram illustrating an exemplary accommodative intraocular lens. [Figure 1C] Figures 1A and 1B show cross-sections of accommodative intraocular lenses. [Figure 1D] This is a top view of an exemplary posterior element of an accommodative intraocular lens. [Figure 1E] This is a cross-sectional assembly diagram of an exemplary optical section of an accommodative intraocular lens. [Figure 2A] This figure shows the deformation of an exemplary support in response to an exemplary force. [Figure 2B] This figure shows the deformation of an exemplary support in response to an exemplary force. [Figure 3] This diagram shows the curing process. [Figure 4] This is a diagram showing the synthesis of the prepolymer. [Figure 5] This is a diagram illustrating an example of a hydrophilic material. [Figure 6] This figure shows the formation of a crosslinked polymer and an exemplary adhesive design. [Modes for carrying out the invention]

[0031] This disclosure generally relates to intraocular lenses, and optionally to accommodative intraocular lenses, and to exemplary materials and their properties for giving the intraocular lens desired properties. The intraocular lenses herein are merely examples of intraocular lenses which may contain any of the materials herein, and this disclosure is by no means limited to the exemplary intraocular lenses herein.

[0032] In some embodiments, the intraocular lens is a accommodative intraocular lens adapted to be placed in the natural lens capsule from which the natural lens has been removed. In some embodiments, the peripheral non-optical portion (i.e., the portion not specifically adapted to focus light onto the retina) can be adapted to respond to deformation of the lens capsule resulting from relaxation and contraction of the ciliary muscle. The response is deformation of the peripheral portion, causing fluids placed in the non-optical and optical portions to move between the peripheral and optical portions, thereby changing the optical parameters (e.g., refractive power) of the intraocular lens. These embodiments are merely examples of optionally accommodative intraocular lenses, which may include any of the materials herein or be manufactured using any method herein.

[0033] Figure 1A is a top view showing a merely exemplary accommodative intraocular lens 10, which includes an optical section 12 and, in this embodiment, a peripheral portion including first and second support sections 14 coupled to the optical section 12 and extending peripherally from the optical section 12. The optical section 12 is adapted to refract light entering the eye onto the retina. The support sections 14 are configured to engage with the lens capsule and are adapted to deform in response to deformation of the lens capsule related to the ciliary muscle. Figure 1B is a perspective view of the intraocular lens 10 showing the optical section 12 and the support sections 14 coupled to the optical section 12.

[0034] The support sections are in fluid communication with the optical section. Each support section has a fluid chamber that is in fluid communication with the optical chamber within the optical section. The support sections are formed of a deformable material and are adapted to deform in response to deformation of the lens capsule related to the ciliary muscle, engaging with the lens capsule. When the support section deforms, the volume of the support section fluid chamber changes, causing the fluids contained in the support section fluid chamber and the optical section fluid chamber to move from the support section fluid chamber to the optical section fluid chamber, or from the optical section fluid chamber to the support section fluid chamber. When the volume of the support section fluid chamber decreases, the fluid moves into the optical section fluid chamber. When the volume of the support section fluid chamber increases, the fluid moves from the optical section fluid chamber to the support section fluid chamber. The flow of fluid in and out of the optical section fluid chamber changes the configuration of the optical section and the refractive power of the intraocular lens.

[0035] Figure 1C is a side cross-sectional view along section AA shown in Figure 1A. The optical section 12 includes a deformable front element 18 fixed to a deformable rear element 20. Each support 14 includes a fluid chamber 22 that is in fluid communication with the optical section fluid chamber 24 of the optical section 12. Only the connection between the left support 14 and the optical section 12 is shown in the cross-sectional view of Figure 1C (though it is unclear). The left support fluid chamber 22 is shown, which is in fluid communication with the optical section fluid chamber 24 by two openings 26 formed in the rear element 20. The right support 14 in Figure 1C is in fluid communication with the optical section chamber 24 by two further openings (not shown) also formed in the rear element at substantially 180 degrees from the shown opening.

[0036] Figure 1D is a top view of the rear element 20 (the front element 18 and support 14 are not shown). The rear element 20 includes a buttress portion 29 in which a channel 32 is formed. The channel 32 enables fluid communication between the optical section 12 and the support 14. An opening 26 is located at one end of the channel 32. Thus, the optical section fluid chamber 24 is in fluid communication with one support through two fluid channels. The buttress portions 29 are configured and sized to be positioned within an opening formed in the support 14 that defines one end of the support fluid chamber, as described below. Each buttress portion 29 includes two channels formed within it. 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.

[0037] Figure 1E is a side view assembly of cross-section AA of the optical section 12, including the front element 18 and the rear element 20 (supports are not shown for clarity). Because the fluid channel 32 is contained within the rear element 20, the rear element 20 must have a structure sufficient to form the channel 32. The buttress portion 29 provides a structure capable of forming the channel 32 internally. At its outermost periphery, the rear element 20 is higher than the front element 18 in the direction from front to rear. In alternative embodiments, the channel may be formed in the front element 18 rather than the rear element 20. The front element would include the buttress portion 29 or other similar structure to provide a structure capable of forming the channel internally. In these alternative embodiments, the rear element can be formed similarly to the front element 18.

[0038] As shown in Figure 1E, the rear element 20 is fixed to the front element 18 at a peripheral surface 28, the peripheral surface 28 is a flat surface extending near the periphery of the rear element 20. Elements 18 and 20 can be fixed to each other using known biocompatible adhesives or adhesives described in other parts of this specification, and using either known methods or methods for bonding the first and second members as described herein. The front element 18 and the rear element 20 can also be formed from a single material to eliminate the need to fix the two elements to each other. In some embodiments, the diameter of the area in which the front element 18 and the rear element 20 are fixed to each other is about 5.4 mm to about 6 mm in diameter.

[0039] The support portion (or, if it is a separate component, another type of peripheral portion) can be attached to the optical portion using any of the adhesives specified herein or any of the methods for bonding the first and second components together as described herein.

[0040] Figures 2A and 2B simply show the placement of an accommodative intraocular lens (shown in Figures 1A-1E) within the eye and how it may respond to the movement of the ciliary muscle. The deformation of at least a portion of the intraocular lens, and the responsiveness of the fluid within it, are influenced by the material selected for the AIOL, as shown in Figures 2A and 2B. The elastic lens capsule "CB" is connected to the ciliary corpuscle "Z", and the ciliary corpuscle "Z" is connected to the ciliary muscle "CM". As shown in Figure 2A, when the ciliary muscle relaxes, the ciliary corpuscle stretches. This stretching is due to a radially outward force "R" resulting from the equatorial configuration of the connection between the lens capsule and the ciliary corpuscle as a whole, pulling the lens capsule in a nearly radially outward direction. The stretching of the ciliary corpuscle results in overall stretching of the lens capsule, causing it to thin. If the natural lens is still present within the lens capsule, it becomes flatter (from anterior to posterior) and radially taller, thereby reducing its refractive power. As shown in Figure 2A, relaxation of the ciliary muscle results in distance vision. However, when the ciliary muscle contracts, as happens when the eye attempts to focus on a near object, the radially medial portion of the muscle moves radially inward, causing relaxation of the ciliary bodies. This is shown in Figure 2B. Relaxation of the ciliary bodies causes the lens capsule to move towards a more curved shape overall, with the anterior surface having a higher curvature than the unaccommodated shape. This results in higher refractive power, allowing the eye to focus on near objects. This is commonly called "accommodation," and the lens is said to be in an "accommodated" shape.

[0041] The radially outer portion 42 is merely an exemplary support portion that directly engages with the portion of the lens capsule connected to the ciliary bodies. The outer portion 42 of the support is adapted to respond to the deformation force "R" applied to the lens capsule substantially radially when the ciliary bodies relax and stretch. This allows the support to deform in response to forces associated with the ciliary muscle (i.e., contraction and relaxation of the lens capsule), resulting in fluid flow between the support and the optical portion in response to the relaxation and contraction of the ciliary muscle. This is shown in Figure 2B. When the ciliary muscle contracts (Figure 2B), the elastic peripheral region of the lens capsule deforms, applying a radially inward force "R" to the radially outer portion 42 of the support 14. The radially outer portion 42 is adapted to deform in response to this deformation of the lens capsule. The deformation reduces the volume of the fluid channel 22, pushing the fluid from the support chamber 22 to the optical chamber 24. This increases the fluid pressure in the optical chamber 42. The increase in fluid pressure causes deformation and increased curvature of the flexible anterior element 18 and the flexible posterior element 20, thereby increasing the refractive power of the intraocular lens.

[0042] The accommodative intraocular lenses described herein may also be fitted to be positioned outside the natural lens capsule. For example, the accommodative intraocular lens may be fitted to be positioned in front of or in the anterior part of the lens capsule after the natural lens has been removed or while the natural lens is still inside the lens capsule, in which case the peripheral portion of the lens is fitted to respond directly to the ciliary muscle rather than relying on deformation of the lens capsule.

[0043] The intraocular lenses described herein, such as the accommodative intraocular lenses shown in Figures 1A to 1E, may have one or more polymer components. For example, in the examples in Figures 1A to 1E, the anterior and posterior components may be made of polymer material. The peripheral portion (e.g., the support portion) may also be made of polymer.

[0044] The polymer materials possess improved resistance to fluid diffusion, a relatively high refractive index, and are adapted to revert to their initial shape after deformation during implantation in the human body. While polymer materials can be used in a variety of applications, their use in ophthalmic devices such as intraocular lenses ("IOLs") is described herein. One use of polymers is in fluid-driven, adjustable IOLs, but polymers can also be used in non-adjustable or non-fluid-driven IOLs. In addition to IOLs, the polymer compositions of the present invention can also be used in other ophthalmic devices, such as, but not limited to, contact lenses, artificial corneas, lens capsule expansion rings, corneal inlays, corneal rings, or other ophthalmic devices. Another exemplary use is in the field of breast augmentation, where polymers can be used as an outer shell-like material to prevent leakage of internal materials.

[0045] The polymer compositions described herein may be used in any of the fluid-driven IOLs described in U.S. Patent Application No. 60 / 433,046 filed December 12, 2002, U.S. Patent Application No. 10 / 734,514 filed December 12, 2003, U.S. Patent Application No. 10 / 971,598 filed October 22, 2004, U.S. Patent Application No. 11 / 173,961 filed July 1, 2005, U.S. Patent Application No. 11 / 252,916 filed October 17, 2005, U.S. Patent Application No. 11 / 642,388 filed December 19, 2006, and U.S. Patent Application No. 11 / 646,913 filed December 27, 2006, the disclosures thereof are incorporated herein by reference in their entirety. However, the composition may also be used in non-fluidically driven IOLs or non-adjustable IOLs.

[0046] Devices implanted in the eye become exposed to fluids within the eye. These intraocular fluids can diffuse through the device over time, potentially causing unintended and / or undesirable effects on its physical properties. For example, polymer IOLs implanted in the eye may have the problem of intraocular fluids diffusing into the polymer material of the IOL. Attempts have been made to coat ophthalmic devices with barrier layers to prevent such diffusion, but these methods can be expensive and time-consuming. Furthermore, if an ophthalmic device contains a fluid-filled chamber or channel within the device, there is a risk that the fluid may escape from the fluid chamber and diffuse into the polymer material. This not only reduces the amount of fluid available to the IOL but can also potentially alter the physical properties of the polymer material. Therefore, the bulk polymers of the present invention described herein may be used in ophthalmic devices to withstand the diffusion of fluids into and from the device.

[0047] For implantable devices that must be implanted through an incision in the sclera, it is generally desirable that the incision in the sclera be as small as possible while still being able to deform the device without damaging it. The device must also be able to deform back to its initial shape after delivery. Therefore, the polymer of the present invention described herein can be used in ophthalmic devices that need to be deformed for delivery through an incision but return to their initial shape immediately after implantation in the eye.

[0048] Similarly, it may be desirable to increase the refractive index ("RI") of an ophthalmic device to enhance its refractive power. Increasing the RI of a bulk polymer can allow for thinner devices while maintaining the desired refractive power. This can also provide a device with a smaller external size at delivery to reduce the size of the eye incision during implantation.

[0049] Improved properties of the polymers described herein include, but are not limited to, elastic modulus, refractive index, resistance to fluid diffusion, composition responsiveness, mechanical strength, stiffness, wettability, and optical clarity. These properties are not necessarily mutually exclusive, and the list is not intended to be exhaustive.

[0050] Some embodiments of this disclosure include polymer materials for ophthalmic devices. The polymer comprises a first component, a second component, and a third or further component. In preferred embodiments, the composition includes butyl acrylate, trifluoroethyl methacrylate, phenylethyl acrylate, and a crosslinking agent, such as ethylene glycol dimethacrylate. These monomers are not intended to be limiting and are shown as examples.

[0051] To obtain the desired properties of the polymer described above, it is possible to select specific monomers or other components to obtain those specific properties, or to select a combination of specific monomers and other components to obtain those specific properties.

[0052] For example, butyl acrylate, a rubbery material, generally enhances the responsiveness of polymer 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. Furthermore, alternatives to butyl acrylate include branched-chain 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.

[0053] In some embodiments, butyl acrylate is present in a range of about 10% to about 80% by volume, and in some embodiments, in a range of about 20% to about 70% by volume. In preferred embodiments, butyl acrylate is present in a range of about 35% to about 65% by volume, and in more preferred embodiments, in a range of about 45% to about 65% by volume. All percentages listed herein are considered to be "by volume" unless otherwise specified.

[0054] In some embodiments, the polymer has an elastic modulus in the range of about 0.1 to about 0.6 MPa. In some embodiments, the elastic modulus is about 0.1 to about 0.3 MPa.

[0055] To enhance the polymer's resistance to fluid diffusion as described herein, trifluoroethyl methacrylate or a suitable alternative may be added to the polymer material. Generally, using monomers with more fluorine atoms will increase the polymer's resistance to fluid diffusion.

[0056] The ethyl group of trifluoroethyl can sometimes bond up to five fluorine atoms, but a large number of fluorine atoms can lower the refractive index of the polymer. Therefore, in some embodiments, trifluoroethyl methacrylate achieves a desirable balance between the polymer's resistance to diffusion and its refractive index.

[0057] Fluorocarbon monomers can enhance the polymer's resistance to fluid diffusion, and some can be used as substitutes for trifluoroethyl methacrylate. Substitutes for trifluoroethyl methacrylate include fluoroacrylates and other monomers that provide polymers with suitable resistance to diffusion properties. Substitutes for 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.

[0058] In some embodiments, trifluoroethyl methacrylate is present in a range of about 5% to about 70%, and in some embodiments, it is present in a range of about 10% to about 50%. In preferred embodiments, it is present in a range of about 15% to about 30%, and in more preferred embodiments, it is present in a range of about 18% to about 22%.

[0059] Phenylate ethyl acrylate, or a suitable alternative, may be included in the polymer composition to increase the refractive index of the polymer. Phenylate groups can generally increase the refractive index of polymers. Alternatives to phenylethyl acrylate include phenyl acrylate and other monomers that provide polymers with a sufficiently high refractive index.

[0060] Other groups that can be used to increase the refractive index of the polymer include, but are not limited to, benzyl(benzoyl), carbazole-9-yl, tribromophenyl, chlorophenyl, and pentabromophenyl. Exemplary monomers that can be used as substitutes for phenylethyl acrylate include, but are not limited to, tribromophenyl acrylate, 2-(9H-carbazole(Carazole)-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.

[0061] In some embodiments, phenylethyl acrylate is present in a range of about 5% to about 60%, while in some embodiments, it is present in a range of about 10% to about 50%. In preferred embodiments, it is present in a range of about 20% to about 40%, and in more preferred embodiments, it is present in a range of about 26% to about 34%.

[0062] In some embodiments, the refractive index of the polymer is about 1.44 to about 1.52. In some embodiments, the refractive index is about 1.47 to about 1.52. In some embodiments, the refractive index is about 1.47 to about 1.5.

[0063] In some embodiments, the composition also includes a crosslinking agent such as ethylene glycol dimethacrylate. 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 acrylate, trifunctional methacrylate, tetrafunctional acrylate, tetrafunctional methacrylate, and mixtures thereof.

[0064] The crosslinking agent may be present in an amount of less than approximately 10%, less than approximately 5%, less than approximately 2%, or less than approximately 1%. The crosslinking agent enables the polymer to interweave in three-dimensional space, resulting in a compact molecular structure with improved elastic memory or responsiveness compared to non-crosslinked compositions.

[0065] In some embodiments of the present invention, the polymer composition also contains one or more ultraviolet (UV) light absorbing substances, such as acrylate or methacrylate-functionalized benzotriazole or benzophenone, in an amount of less than 5%. In some embodiments, the UV absorbing substance is present in an amount ranging from about 0.05% to about 2%. Suitable UV absorbers for use in the present invention include, but are not limited to, β-(4-benzotriazol-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- Examples include chlorobenzotriazole, 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-chlorobenzotriazole, and 2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropoxy)phenyl]-5-chlorobenzotriazole. Those skilled in the art will recognize that a variety of other chemicals may be selected as ultraviolet absorbers.

[0066] One or more suitable free radical thermal polymerization initiators may be added to the polymer compositions 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-butylperoxypivalate, and peroxydicarbonate. Such initiators may be added in an amount ranging from about 0.01% to about 1% of the total polymer mixture.

[0067] Alternative UV initiators include, but are not limited to, those known in this field, such as benzoin methyl ether, benzoin ethyl ether, Darocur® 1173, 1164, 2273, 1116, 2959, 3331 (EM Industries), and Irgacur® 651 and 184 (Ciba-Geigy, Basel, Switzerland).

[0068] 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 located within the device (such as a fluid chamber located within a fluid-driven adjustable 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 fluorocarbon material or polymer, examples of which include hexafluoroethane, hexafluoropropylene, hexafluoropropane, octafluoropropane, polytetrafluoroethylene, and 1H,1H,2H-perfluoro-1-dodecene. The barrier layer may be attached or covalently bonded to the solid surface of the ophthalmic device individually or in combination by various manufacturing processes. One common manufacturing process is plasma deposition.

[0069] The layers formed by plasma deposition are generally very thin, for example, about 20 to 100 nanometers thick. Since fluorocarbon polymers generally have a low refractive index, a barrier layer with a thickness of less than one-quarter the wavelength of visible light becomes invisible to the naked eye.

[0070] As described above, the polymers of the present invention described herein may be used in IOLs in which a fluid is placed inside, for example, in a fluid chamber. Generally, the viscosity of a fluid is related to its diffusion properties. Fluids with low viscosity can diffuse more easily through the polymer.

[0071] Ophthalmic devices may contain silicone oil. The amount of silicone oil that diffuses 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 from silicone oil. Generally, low molecular weight components will diffuse faster than high molecular weight components. However, high molecular weight components contribute to increased viscosity, requiring greater force to deliver the fluid throughout the IOL. Therefore, silicone oil with a narrow molecular weight distribution is preferred. The fluid placed in the ophthalmic device is not limited to silicone oil and may be, for example, saline solution.

[0072] However, in some embodiments, the IOL components are substantially refractive index matched such that a single deflection of the IOL surface contributes significantly to any change in refractive power during adjustment. For example, a bulk polymer would be substantially refractive index matched to any fluid within the IOL. A substantially refractive index matched state, when that expression is used herein, includes a small difference in refractive index between the components of the IOL. For example, if adhesives are used in the manufacture of the IOL, those adhesives may have different refractive indices, but the difference is negligible when considering the overall change in refractive power of the adjustable IOL.

[0073] In some embodiments, the polymer T G Its temperature is approximately -20°C, and it can stretch to about four times its length without breaking.

[0074] The optical and support parts may be composed of the same polymer composition, or they may be composed of different compositions. The composition of the optical and support parts may be determined by the desired properties of each component. For example, since the support part generally does not contribute to the focusing of light, it may not be necessary to achieve a high refractive index in the support part, and therefore the polymer used in the support part does not need to have a high refractive index. Similarly, for example, it may be desirable for the support part to have a different response than the static optical part.

[0075] The following non-limiting examples illustrate specific aspects of the present invention. [Example 1]

[0076] Combine the following ingredients and mix well.

[0077] [Table 1]

[0078] The polymer can be manufactured by pouring the mixture into a mold and curing the polymer by either UV light or heat curing. The resulting polymer had a swelling rate of 0 in silicone oil, a refractive index of 1.477, and an elastic modulus of 0.163 MPa. [Example 2]

[0079] The following ingredients can be added together, thoroughly mixed, and then processed in the same way as the ingredients in Example 1.

[0080] [Table 2]

[0081] The resulting polymer had a swelling coefficient of 0.019, a refractive index of 1.473, and an elastic modulus of 0.27 MPa.

[0082] While the embodiments described above illustrate exemplary polymer formulations, further exemplary formulations with higher refractive indices are shown below. Increasing the refractive index may be desirable to increase the basic refractive power of the intraocular lens. In some embodiments, the refractive index of the polymer material of the intraocular lens is approximately 1.48 to approximately 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 percentage of the polymer. Other components may be modified to offset the increase in the concentration of monomers containing phenyl groups. Table 1 (Table 3) below shows further exemplary polymer formulations for use in ophthalmic devices and their components, where the refractive index is higher than in some of the embodiments described above. The first three formulations have refractive index values ​​very close to 1.5180 at 532 nm and 35°C, which is an example of an RI of 1.50 to 1.53. The fourth formulation is similar to some of the examples described above. All four formulations in Table 1 (Table 3) contain BA, PEA, and TFEMA.

[0083] A typical and significant advantage of the exemplary formulations in Table 1 (Table 3) is their dramatically reduced tendency to swell when exposed to silicone fluids commonly used in some fluid-driven accommodative intraocular lenses, such as those incorporated herein by reference (including relatively high refractive indices). The data support this reduced swelling, which manifests as significantly improved refractive power stability and the potential for accelerated aging testing without the refractive power reduction caused by swelling seen in some fluid-driven accommodative intraocular lenses.

[0084] [Table 3]

[0085] Compositions 1-3 in Table 1 (Table 3) can be used, for example, in the optical portion of an accommodative intraocular lens ("AIOL") (accommodative intraocular lenses are fluid-driven) or in the peripheral portion of an AIOL.

[0086] The specific monomers shown herein are provided merely as examples, and the scope of this disclosure is not limited in this way. For example, in some embodiments, the percentage of BA is 2 to 20%, for example, 3 to 17%. In some embodiments, the percentage of PEA is 50 to 80%, for example, 60 to 75%. In some embodiments, the percentage of TFEMA is 10 to 35%, for example, 15 to 30%.

[0087] The first three formulations in Table 3 (Table 5) are also examples of polymer materials containing alkyl acrylates present in amounts of 3% to 20%, fluoroacrylates present in amounts of 10% to 35%, and phenyl acrylates present in amounts of 50% to 80%.

[0088] Polymer materials can be manufactured using various manufacturing processes, including curing. Figure 3 shows an exemplary method for curing three monomers (i.e., BA, PEA, and TFEMA), a UV blocking agent, and a crosslinking agent, such as EGDMA, to obtain a cured polymer material containing the three monomers. Any of the polymer materials can be manufactured by this method.

[0089] Figure 4 shows an alternative manufacturing process in which a prepolymer is first made from multiple monomers (in this example, they are the same as those in Figure 3, but do not have to be the same), and the prepolymer is not yet crosslinked (not yet fully cured), as shown in Figure 4. The monomer is first combined with a monomer containing a hydroxyl moiety, which is then converted to a crosslinkable methacrylate, thereby enabling the crosslinkable polymer to fully cure. 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 exemplary Figure 4. Figure 6A shows an exemplary method for making a crosslinkable polymer from a prepolymer (e.g., the prepolymer in Figure 4), in which the hydroxyl moiety is converted to a methacrylate (bottom right of Figure 6A), which can then be crosslinked to form a cured polymer material, which can be used to make any of the exemplary IOL components described herein.

[0090] As will be described in more detail with respect to the consideration of adhesives (which is fully incorporated into this section of the disclosure), crosslinkable polymers such as those described above can be combined with hydrophilic reactive diluents. When hydrophilic monomers (e.g., HEMA, HBA) are used as reactive diluents for crosslinkable polymers, curing results in an interpenetrating network structure in the polymer matrix containing hydrophilic homopolymers as a second phase. Long-chain homopolymer "blocks" can enhance the effectiveness of functional groups associated with the hydrophilic components in random copolymers. In some embodiments, polymers are developed by using about 25-35% (e.g., 30%) of HEMA or HBA as a reactive diluent for the crosslinkable polymer. In some exemplary manufacturing methods, no phase separation occurred upon curing, and the cured polymer material was transparent. These crosslinkable polymer-based formulations are very suitable for the production of high-precision (very low shrinkage) parts that are directly molded, such as in support and optical parts or any of the adjustable intraocular lenses described herein or incorporated herein by reference.

[0091] A more typical advantage of incorporating one or more hydrophilic monomers (e.g., HEMA, HBA) into polymer materials as reactive diluents is the reduction of haze or greasiness caused by water (i.e., water bubbles in the material).

[0092] Figures 5A and 5B show exemplary polymerization of hydrophilic materials, with HEMA shown in Figure 5A and HBA in Figure 5B.

[0093] glue

[0094] One aspect of this disclosure describes an adhesive that can be used to bond first and second polymers, and optionally first and second polymers of an intraocular lens, to each other. While this disclosure describes adhesives and polymers for use in ophthalmic applications, it is not intended to limit them thereto. The materials described herein can be used in other suitable applications. The exemplary polymer materials described above (e.g., Examples 1, 2, and Table 1 (Table 3)) are merely examples of polymer formulations for first and second components to be bonded to each other. The adhesives described herein will be described in relation to the polymers described herein, but the concepts herein are applicable to other polymer materials and other adhesives. The examples shown herein are illustrative only, and this disclosure is not intended to limit it to any particular adhesive or particular polymer described herein.

[0095] During the manufacture of certain ophthalmic devices, two or more polymeric objects are bonded or glued to each other. The bond should be strong enough to ensure that the two or more objects remain bonded to each other during use and during implantation surgery. For example, the bond must be maintained even if the device needs to be reconfigured or deformed when it is implanted and / or delivered into the eye. Furthermore, the presence of the adhesive should not cause the optical clarity of the device to decrease to an unacceptable level in or near the adhesive. The adhesive-polymer combinations described herein not only maintain an acceptable level of optical clarity but also improve or maintain the mechanical integrity of the adhesive / polymer bond.

[0096] One aspect of the present disclosure is an adhesive having a first component which is the same or substantially the same material as, or substantially similar in properties to, first and second polymeric objects that are bonded together. The first and second objects may instead have different formulations. As used herein, the adhesive is used to bond the “first object” to the “second object”.

[0097] In some embodiments, the first and second objects are first cured and then bonded to each other using the bonding techniques described herein.

[0098] In some embodiments, the adhesive comprises first and second main components and a curing additive (e.g., a photoinitiator). In purely exemplary embodiments, including exemplary manufacturing methods, the first main component (e.g., about 50–75%) is a crosslinkable polymer ("CLP"; the above consideration of crosslinkable polymers is incorporated into this aspect of the present disclosure) having the same or similar composition as the first and second objects, or substantially similar properties. Since the CLP is not yet crosslinked, it behaves as a fluid, soluble, thermoplastic material rather than a thermosetting material. The CLP then combines with a reactive acrylic monomer diluent (e.g., ADMA, as shown in Figure 16, e.g., about 20–50%), which is the second main component, and the remaining component is about 2% photoinitiator for curing the adhesive. At the junction line between the first and second objects, the CLP is so large / bulky that it cannot move into either object, while the reactive acrylic monomer diluent and photoinitiator can move / diffuse across the junction line into both curable polymeric objects. Depending on time, temperature, and the thickness of the junction line, the reactive acrylic monomer diluent and initiator diffuse to a certain degree (controllable), and then cure (e.g., by ultraviolet light) to form an already crosslinked polymer (having the same or similar properties as the first and second objects) which also contains the interpenetrating network structure of the reactive acrylic monomer diluent (e.g., ADMA) in the first and second objects, as well as the network structure of the permeated reactive acrylic monomer diluent. If the degree of diffusion is such that the concentration of the reactive acrylic monomer diluent is essentially the same across and within the junction line, the properties of the material will be substantially the same across the region.

[0099] In some embodiments, the first main component (which may have the same or similar composition as the first and / or second substance) constitutes about 55% to about 80% (e.g., about 55% to about 75%) of the adhesive. In some embodiments, the second main component (reactive acrylic monomer diluent) constitutes about 18% to about 43% (e.g., about 23% to about 43%) of the adhesive.

[0100] The adhesives described herein offer several mechanical advantages. Generally, the bond strength improves over time, which extends the service life of the device. When substantially the same or substantially similar materials are used, a cross-penetration network structure is formed between the polymer and the adhesive, resulting in an adhesive material that is substantially identical throughout. Furthermore, the mechanical and thermal properties of the materials can also be substantially the same. For example, the elastic moduli of the polymer and the adhesive can be designed to be the same or substantially the same. In addition, the surface energy can be substantially the same, which helps to retain ambient water from the adhesive and prevents water from moving into the device and forming droplets.

[0101] Furthermore, when the first component of the adhesive is the same as 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 little to no shrinkage because it can essentially be considered the last 1% of all pre-cured material, and therefore the more CLP used in the adhesive formulation, the less shrinkage the formulation will exhibit upon curing. In addition, if ADMA, for example, diffuses into the bonded acrylic, the accompanying swelling may occur, which can offset some or all of the shrinkage caused by curing.

[0102] In one embodiment of this disclosure, the term “substantially identical” is intended to include compositions having nearly the same amount of the same or similar components, or having substantially identical properties. In some embodiments, the term “substantially identical” may refer to compositions that contain the same components, where the percentage of each component, by weight or volume, is within the range of 1 to 50% of the components of the composition being compared. In other embodiments, “substantially identical” may be used to refer to compositions having substantially the same physical properties (e.g., viscosity, refractive index, structure, etc.).

[0103] Furthermore, there are optical advantages to using an adhesive material containing a first component that is the same as or substantially the same as the polymeric object material. As shown above, the surface energy may be substantially the same, and there are substantially no hydrophobic areas. Substantially the same surface energy prevents the formation of water droplets, which prevents a decrease in optical clarity. Moreover, by using substantially the same material, the refractive index of the adhesive and the bonded polymer can be made substantially the same. While a difference in refractive index between the adhesive and the polymer does not cause significant optical disturbance, creating materials with substantially the same refractive index can reduce the possibility of such disturbance.

[0104] The crosslinkable polymer in the adhesive does not need to have the same formulation (same monomers and percentages) as the polymer formulations of the first and / or second polymeric objects to be bonded together, or even have the same monomers. While it is advantageous for the crosslinkable polymer formulation to have similar properties to the formulations of the first and / or second polymeric objects described above, in other embodiments they can be quite different. Simply as an example, formulation #4 in the table is used as a crosslinkable polymer in an adhesive formulation and is used to bond polymeric objects having formulations such as those shown in formulations #1 to #3 in Table 1 (Table 3). In this example, both the crosslinkable polymer in the adhesive and the polymer formulations of the first and second objects 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 in the adhesive and the polymer formulations of the first and second objects may be the same.

[0105] Any intraocular lens including first and second members that are bonded to each other can be bonded to each other using the concepts of this specification.

[0106] In some embodiments, an adhesive is formed and a crosslinkable polymer is formed according to the method shown in Figure 16 above. That is, a prepolymer is used to form a crosslinkable polymer, which can be cured together with the first and second materials when mixed with a reactive diluent (e.g., ADMA).

[0107] The disclosures herein also describe exemplary fluids that can be used with intraocular lenses. In some embodiments, the fluid is a silicone oil, and in some embodiments, the intraocular lens is a comorbid intraocular lens.

[0108] Ophthalmic devices may contain one or more silicone oils. Silicone oils may be used in accommodative intraocular lenses that use fluid transfer to change the refractive power of the IOL. Silicone oils may also be used in non-accommodative intraocular lenses. When silicone oils are used in accommodative IOLs containing bulk materials such as polymer materials, some of the oil components can pass through the bulk material, causing swelling of the bulk material. Therefore, the selected silicone oil or oil prevents undesirable swelling of the bulk polymer. Exemplary polymer materials that can be used in the bulk material of the IOL can be found herein.

[0109] 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. Low molecular weight components in the silicone oil can be removed using a series of stripping methods. Generally, low molecular weight components diffuse faster than high molecular weight components. However, high molecular weight components contribute to increased viscosity, requiring greater force to deliver the fluid throughout the IOL. Therefore, a silicone oil with a narrow molecular weight distribution is preferred. The fluid placed within the ophthalmic device is not limited to silicone oil; it could be, for example, saline solution.

[0110] One property of silicone oils that helps ensure a sufficient response and prevents undesirable swelling is the polydispersity index ("PDI") of the silicone oil intended for use in IOLs. PDI is generally an indicator of the molecular weight distribution of a given sample. 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 other examples, the PDI of the silicone oils is less than about 1.2.

[0111] A second characteristic of silicone oil that helps ensure a sufficient response and prevents undesirable swelling is its average molecular weight. When high concentrations of relatively low molecular weight components are present in the silicone oil, more of these low molecular weight components pass through to the bulk material of the IOL, causing swelling of the bulk material. To prevent undesirable swelling, the concentration of relatively low molecular weight components should be minimized. By reducing the concentration of relatively low molecular weight components and maintaining high concentrations of relatively high molecular weight components, fewer low molecular weight components will pass through to the bulk polymer material, thereby reducing the amount of swelling that occurs in the bulk material.

[0112] The PDI of a silicone oil and its average molecular weight are related. By lowering the PDI of the silicone oil while providing a silicone oil containing high concentrations of relatively high molecular weight components and low concentrations of low molecular weight components, the IOL response is maintained (by providing a silicone oil with appropriate viscosity) and undesirable swelling is avoided. Furthermore, providing a silicone oil with low PDI and very low concentrations of low molecular weight components means that the silicone oil has a molecular weight of the minimum size necessary to prevent polymer swelling.

[0113] In some embodiments, silicone oils are provided having 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 within this range are large enough to substantially prevent swelling of bulk polymer materials. This is preferable to alternative methods that use higher molecular weight silicone oils, which essentially have fewer low molecular weight components, because almost all the molecules that make it up are large. Thus, high molecular weight silicone oils can have high viscosity, which can shorten the response time of the adjustable IOL.

[0114] The silicone oils described herein have very low concentrations of relatively low molecular weight components. The very low molecular weight components are present in amounts of less than about 200 ppm of each component, and in some embodiments, less than about 100 ppm. In some specific embodiments, the very low molecular weight components are present in amounts of less than about 50 ppm.

[0115] Examples of relatively low molecular weight components include those with a molecular weight of approximately 1000 daltons or less. For example, in some embodiments, the concentration of components with a molecular weight of approximately 1000 daltons or less is approximately 50 ppm or less.

[0116] In one particular embodiment, a silicone oil is provided in which 20% or less of the total silicone consists of components with a weight of less than approximately 4000 Daltons; 10% or less of the total polymer fluid by weight consists of components with a weight of less than 3000 Daltons; and 50 ppm or less consists of any component with a weight of less than 1000 Daltons.

[0117] The estimated molecular weights and polydispersity values ​​described herein are relative to polystyrene molecular weight standards.

[0118] Silicone oils generally need to be designed in a way that prevents harmful interactions with surrounding bulk IOL materials in some IOLs, such as swelling, fogging, dissolution, or reactions with other materials (e.g., polyacrylate). The solubility of silicone oil in bulk materials is determined by the chemical structure and molecular weight distribution of the silicone oil. Other parameters that influence this interaction include the composition and properties of the bulk material, such as homogeneity, chemical structure, hydrophobicity, modulus of elasticity, and crosslinking density.

[0119] Generally, the viscosity of the silicone oil must be specified and minimized because, in embodiments where the fluid-driven adjustable IOL operates dynamically, the IOL needs to have an appropriate response time. In some embodiments, the viscosity of the silicone oil is 2400 cP or less.

[0120] In some embodiments, the silicone oil is made from a cyclotrisiloxane containing a ratio of two dimethylsiloxane units to one diphenylsiloxane unit. In some embodiments, the oil is at least 95% (e.g., 100%) of a single cyclotrisiloxane containing a ratio of two dimethylsiloxane units to one diphenylsiloxane unit.

[0121] In some embodiments, the oil is a copolymer of diphenylsiloxane and dimethylsiloxane, comprising about 20% diphenylsiloxane and about 80% dimethylsiloxane.

[0122] 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 more. In these embodiments, the refractive index of the silicone oil is approximately 1.5180, which is an example of 1.50 to 1.53. In some embodiments, a silicone oil that is approximately 100% diphenylsiloxane can be used in accommodative intraocular lenses having formulations such as #1 to #3 in the table above. In these embodiments, the fluid and polymer were refractive index matched to approximately 1.518.

[0123] In some embodiments, the average molecular weight of the diphenylsiloxane polymer compound is approximately 4500 to 6500 daltons.

[0124] In some IOLs, it is desirable to avoid creating an optical interface between the bulk material of the IOL and the silicone oil within the IOL. This can be achieved by refractive index matching the silicone oil to the bulk material of the IOL (which in some embodiments is a polymer material). As used herein, “refractive index matching” refers to minimizing the optical interface between the first and second media. For example, refractive index matching of silicone oil and polymer material refers to an attempt to eliminate the optical interface between them, and “substantially the same” refers to refractive indices that are intended to be as close as possible to minimize the difference in refractive indices, even if they are slightly different.

[0125] In some embodiments, where the silicone oil is refractive index-matched to the bulk polymer material, the refractive index of the silicone oil is approximately 1.47 to approximately 1.55, and in some embodiments, it is approximately 1.50 to approximately 1.53.

[0126] In some embodiments, the silicone oil needs to be able to be filtered through a filter of about 0.7 microns. In some embodiments, the percentage of volatile substances is less than about 0.2%. In some embodiments, the silicone oil has a refractive index unit of about 0.035 or less in the visible range of 400 nm to 750 nm at 35°C. In some embodiments, the components of the silicone oil are completely miscible with no signs of phase separation (i.e., clouding or suspension). In some embodiments, the silicone oil has a transmittance of more than 85% for a fluid sample about 1 cm thick in the range of 400 nm to 1100 nm.

[0127] Furthermore, the silicone oil should be transparent, colorless, contain less than approximately 10 ppm of heavy metals and other insoluble inorganic impurities, and be substantially free of silanols.

[0128] Silicone oil synthesis

[0129] The molecular weight, polydispersity, and sometimes refractive index of silicone oils can be controlled by the methods used to synthesize and purify them. The viscosity of the oil is related to its molecular weight, polydispersity, and the structure of the bulk polymer, all of which are influenced by the synthesis and purification of the polymer. However, the target viscosity cannot be arbitrarily selected, independent of the target molecular weight, polydispersity, composition, and structure of the silicone oil. A common class of polymer synthesis reactions known as "living polymerization" can provide the degree of control necessary to help meet some of the design requirements of silicone oils.

[0130] The term "living polymerization" refers to polymerization reactions that do not undergo numerous chain termination or chain transfer side reactions. The absence of side reactions makes it possible to use living polymerization to synthesize a variety of materials that are difficult to prepare by other methods. This class of polymerization reactions can be used to prepare a variety of 1) structural polymers—including linear, star-shaped, and comb-shaped polymers; 2) compositions—homopolymers, random copolymers, block copolymers, and graft copolymers; and 3) functionalized polymers—polymers with one- and two-ended functionalized polymers, as well as side-chain functionalized polymers. This class of polymerization reactions can often be used to prepare polymers with narrow molecular weight distributions at various molecular weights. As a result, living polymerization is often employed when polymers with specific structures and compositions are required. For example, polymers with broad molecular weight distributions can be considered mixtures of many compounds, and the properties of the material are some function of that distribution. However, polymers with narrow molecular weight distributions, such as those obtained from living polymerization, can be considered "pure" samples with better defined properties.

[0131] Anionic and cationic living polymerizations have been described in the art. More recently, radical living polymerization has been developed. In one example of anionic synthetic routes, the use of alkyllithium compounds in the ring-opening polymerization of cyclotrisiloxanes is considered a “living” polymerization, allowing for the degree of control necessary to produce the silicone oils described above. By changing the ratio of phenyl-containing cyclotrisiloxane to methyl-only cyclotrisiloxane (i.e., preparation of random block copolymers), the refractive index of the silicone oil can be varied between the refractive indices of both pure homopolymers alone (i.e., between pure diphenylpolysiloxane and pure dimethylpolysiloxane).

[0132] As another example, the refractive index of a silicone oil composition can be changed by varying the ratio of tetramethyl-diphenyl-cyclotrisiloxane to hexamethylcyclotrisiloxane. By varying this ratio, a range of refractive indices from approximately 1.40 to 1.54 can be achieved, including refractive indices of approximately 1.47 to 1.49.

[0133] As described above, living polymerization also offers the advantage of being able to prepare polymer products of a target molecular weight. This can be achieved by changing the monomer-to-initiator ratio during the polymerization reaction, which can be applied to the preparation of specific amounts of silicone oil.

[0134] The narrow molecular weight range of the products is also an advantage that can be realized in the preparation of silicone oils because only a smaller amount of low molecular weight oligomers are formed during the polymerization reaction. A smaller amount of low molecular weight material prepared minimizes the amount of purification that needs to be performed later 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 formed during the polymerization reaction, it is easier to extract the low molecular weight material when purifying the synthetic silicone oil using supercritical CO2 extraction (described below), resulting in a higher yield of the desired product.

[0135] While the viscosity of a polymer is not directly related to the method of preparation, 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-shaped" polymers, "star-shaped" polymers, and other branched structures can be prepared, and these may have different physical properties (e.g., viscosity) due to the different physical shapes of their structures, even if they have a chemical composition very similar to "linear" polymers. The preparation of highly branched silicone oils can produce products with significantly lower viscosity than linear silicone oils with the same molecular weight.

[0136] Silicone oils can also be prepared using other synthetic methods, such as base-catalyzed ring-opening of cyclotrisiloxane and condensation of dialkyldichlorosilane with water. While these synthetic methods can also produce silicone oils with many of the above properties, they may require more effort for purification.

[0137] Refinement of silicone oil

[0138] Silicone oil can be purified by various methods. The silicone oil obtained after the polymerization reactions discussed above may contain silicone oil polymer derivatives with varying molecular weights. Low molecular weight silicone oil can cause undesirable swelling of bulk polymer materials and should be minimized. Wiped film evaporation can be used to remove low molecular weight compounds with high boiling points. However, silicone oil products may discolor due to excessive heating when using wiped film evaporation.

[0139] Supercritical CO2 extraction is one exemplary purification method that can be used to selectively remove fractions of silicone oil based on molecular weight and chemistry. Supercritical CO2 extraction for purifying silicone oil to produce silicone retinal vitreous tamponade 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, and not in fluid-driven adjustable IOLs in particular. Pressure, temperature, extraction rate conditions, and the use of co-eluting solvents such as acetone can be varied to obtain fractions with a narrow molecular weight distribution (i.e., low PDI). The mixture can be separated in such a way that very low molecular weight and very high molecular weight fractions are removed from the sample to obtain the desired molecular weight. Since the supercritical extraction conditions can be varied to obtain separation based on chemistry, this purification method can also be used to obtain a desired refractive index. Thus, supercritical CO2 extraction can be used, for example, to produce silicone oil having substantially the same refractive index as the bulk polymer intended for use in intraocular lenses (e.g., fluid-driven adjustable intraocular lenses).

[0140] Tables 2 (Table 4) to 4 (Table 6) show exemplary data obtained by supercritical CO2 extraction of sample silicone oil.

[0141] [Table 4]

[0142] [Table 5]

[0143] [Table 6]

[0144] Similarly, size exclusion chromatography on a preparation scale is an alternative method for fractionating polymer samples into their molecular weight components. Fractional precipitation of silicone oil may also be used to separate the components of the resulting polymer.

[0145] The removal of silicone oil components that dissolve in bulk IOL material over time (e.g., during storage) may be achieved by exposing the bulk amount of IOL material, or other material selected for that purpose, to silicone oil. When stored with suitable materials, the silicone oil components that dissolve in bulk IOL polymer material can be removed by adjusting the ratio of silicone oil to polymer adsorbent so that those materials remain in the oil at sufficiently low levels.

[0146] An important aspect of the fractionated oils described herein is very low polydispersity ("PDI") (e.g., less than 1.5, less than 1.3, or even less than 1.2) that has not been attainable by other known polymerization methods. One method for obtaining desired properties that have not been achieved in the past is to fractionate the oil after synthesis to remove very low molecular weight portions (and sometimes very high molecular weight portions as well). Very low PDI offers the advantage of adapting the material properties to functional properties; in particular, high molecular weight (and therefore low swelling and refractive strength stability) and low viscosity (and therefore fast regulated and unregulated response times). A further benefit of some embodiments herein, including blended high-refractive-index and low-refractive-index oil components, such as those shown in Table 5 (Table 7) and Table 6 (Table 8) below (e.g., blended dimethylsiloxane versus diphenylsiloxane), is that, despite the high molecular weight of the fractionated oils, the blended refractive index-matched system (refractive index-matched with the polymer material of the lens) does not significantly increase viscosity due to changes in the blend ratio, which are linked to changes in intrinsic viscosity as a function of the component content (e.g., the oil components are dimethylsiloxane and diphenylsiloxane).

[0147] Tables 6 (Table 8) and 7 (Table 9) show examples of unfractionated and fractionated blends (high RI and low RI) of exemplary silicone oils, respectively. The exemplary blended oils in Tables 5 (Table 7) and 6 (Table 8) have a viscosity of less than 1000 cPs and a blended refractive index of 1.47 to 1.50.

[0148] [Table 7]

[0149] [Table 8]

[0150] One exemplary method for producing oils with very low PDI is by using a fractionation method that is robust, highly reliable, reproducible, scalable, and high-precision. The fractionation method allows for the property matching of silicone fluids to acrylic materials for lenses that cannot be achieved by other methods, thereby minimizing the shift in refractive force due to swelling, while maintaining a desirable low-viscosity fluid that allows for an acceptable fast response time, both of which are described herein.

[0151] An exemplary method is a high-temperature isopropyl alcohol / water fraction. The only reagents used are isopropyl alcohol and water, which can be removed from the oil by evaporation.

[0152] In exemplary embodiments, the oil comprises a blend of dimethylsiloxane and diphenylsiloxane, examples of which are described herein in 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.

[0153] Table 7 (Table 9) lists exemplary silicone oils, including their average molecular weight, polydispersity, and predicted diffusion. All of these examples have polydispersity values ​​less than 1.3, and this is an example of a value less than 1.5.

[0154] [Table 9]

[0155] Table 8 (Table 10) lists exemplary silicone oils, including changes in average molecular weight, polydispersity, and refractive index. All of these examples have polydispersity values ​​less than 1.3, and this is an example of a value less than 1.5.

[0156] [Table 10]

[0157] In some embodiments, the average molecular weight of the oil is approximately 4500 Da to 6500 Da, and in some embodiments, it is 5000 Da to 6000 Da, for example, approximately 5200 Da to 5800 Da. In some embodiments, the viscosity is less than 2400 cPs.

[0158] While silicone oils used in adjustable IOLs are primarily described herein, any silicone oil can be used in non-adjustable IOLs. For example, a non-adjustable IOL may have a relatively rigid outer polymer shell surrounding a silicone oil core. Swelling of the bulk polymer material must also be taken into consideration, and therefore the desired silicone oil manufacturing methods described herein can be utilized.

[0159] In some embodiments of U.S. Patent Publication 2013 / 0131794, the accommodative intraocular lens includes an optical section comprising an anterior lens element and a posterior lens element defining an optical fluid chamber. In some embodiments, the fluid can be substantially refractive index-matched with the materials of the anterior and posterior elements (creating an optical section that essentially behaves like a single lens), while in some embodiments, the fluid has a different refractive index from one or both of the anterior and posterior lens elements. By introducing the fluid into the optical chamber with different refractive indices, two further optical interfaces can be created within the optical section (anterior lens element / fluid interface and fluid / posterior lens element interface). By providing these further optical interfaces, it is possible to have greater control over the refractive power of the IOL throughout the entire accommodation process. The following are examples of embodiments of the present invention. [Embodiment 1] An intraocular lens comprising a polymer material containing butyl acrylate present in an amount of 2% to 20%, trifluoroethyl methacrylate present in an amount of 10% to 35%, and phenylethyl acrylate present in an amount of 50% to 80%. [Embodiment 2] An intraocular lens according to Embodiment 1, wherein the refractive index of the polymer material is 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] The intraocular lens according to Embodiment 1, wherein a polymer material defines a fluid channel, and the intraocular lens further contains silicone oil in the fluid channel. [Embodiment 5] The intraocular lens according to Embodiment 4, wherein the silicone oil is refractive index matched with the polymer material. [Embodiment 6] The intraocular lens according to Embodiment 4, wherein the polydispersity of the silicone oil is less than 1.2. [Embodiment 7] Alkyl acrylates present in amounts of 3% to 20%; Fluoroacrylate present in amounts of 10% to 35%; Phenyl acrylate, which is present in amounts of 50% to 80%, Polymer materials for ophthalmic devices, including [specific material]. [Embodiment 8] An optical section containing a polymer material, adapted to refract light onto the retina; A silicone oil with a polydispersity index of less than approximately 1.2 is placed inside the optical section. Includes accommodative intraocular lenses. [Embodiment 9] The adjustable intraocular lens according to Embodiment 8, wherein the average molecular weight of the silicone oil is 4500 to 6500. [Embodiment 10] The adjustable intraocular lens according to Embodiment 8, wherein the viscosity is 2400 cP or less. [Embodiment 11] The adjustable intraocular lens according to Embodiment 8, wherein the silicone oil contains diphenylsiloxane units. [Embodiment 12] The adjustable intraocular lens according to Embodiment 8, wherein the silicone oil is made of cyclotrisiloxane containing a ratio of two dimethylsiloxane units to one diphenylsiloxane unit. [Embodiment 13] The accommodative intraocular lens according to Embodiment 8, wherein the refractive index of the silicone oil is 1.47 to 1.53, and optionally 1.50 to 1.53. [Embodiment 14] An adhesive for accommodative intraocular lenses, comprising a first component having properties that are the same as or substantially similar to those of the polymer material of a first object of the accommodative intraocular lens. [Embodiment 15] The adhesive according to Embodiment 14, comprising a first component which is the same as the polymer material of the first object of the intraocular lens. [Embodiment 16] The adhesive according to Embodiment 15, comprising a first component containing a monomer present in the polymer material. [Embodiment 17] The adhesive according to Embodiment 14, comprising a second main component which is a reactive acrylic diluent. [Embodiment 18] The adhesive according to Embodiment 14, comprising a first component that is not the same as, but substantially similar to, the polymer material of a first object of an accommodative intraocular lens. [Embodiment 19] A method for manufacturing an accommodative intraocular lens, A process for curing the first and second components of an accommodative intraocular lens; A step of applying an adhesive between the first member and the second member, comprising a first component having the same, substantially the same, or substantially similar properties as at least one of the first and second members, and further comprising a second main component which is a reactive acrylic diluent. Methods that include... [Embodiment 20] A method for producing a polymer component of an intraocular lens containing multiple monomers, A step of forming a polymer prepolymer containing multiple monomers; The process of curing the prepolymer to form polymer components and Methods that include... [Embodiment 21] The method according to Embodiment 20, wherein the step of forming a prepolymer includes a step of compounding a plurality of monomers with a monomer containing a hydroxyl moiety. [Embodiment 22] The method according to Embodiment 21, further comprising a step of producing a crosslinkable polymer from a prepolymer, wherein the step of producing the crosslinkable polymer includes a step of changing the hydroxyl portion to a methacrylate portion. The following are also included as aspects of this disclosure: [Aspect 1] A method for manufacturing at least one of the support portion and the optical portion of an intraocular lens, The combination involves combining multiple monomers with additional monomers containing a hydroxyl moiety, wherein the multiple monomers include butyl acrylate, trifluoroethyl methacrylate, and phenylethyl acrylate. To form at least one of the support portion and the optical portion of the intraocular lens, the plurality of monomers and the additional monomers are cured, converting the hydroxyl portion to a crosslinkable methacrylate, and curing. Methods that include... [Aspect 2] The method according to embodiment 1, wherein the additional monomer containing the hydroxyl portion is hydroxyethyl methacrylate (HEMA). [Aspect 3] The method according to embodiment 1, wherein the additional monomer containing the hydroxyl portion is hydroxyethyl acrylate (HEA). [Aspect 4] The method according to embodiment 1, wherein the additional monomer containing the hydroxyl portion is hydroxybutyl acrylate (HBA). [Aspect 5] The method according to embodiment 1, wherein the additional monomer containing the hydroxyl portion is added to reduce haze or greasiness caused by water. [Aspect 6] The method according to embodiment 1, wherein curing includes UV curing in the presence of a photoinitiator. [Aspect 7] A method for manufacturing an intraocular lens, To form the first body and the second body of the intraocular lens, The adhesive is applied between the first body and the second body, wherein the adhesive is A first main component having the same, substantially the same, or substantially similar properties as the polymer material constituting the first body or the second body, wherein the first main component is present in the adhesive in an amount between 55% and 80%, and The second main component is applied to the skin, The first body is bonded to the second body by curing the adhesive, wherein the adhesive, upon curing, creates a reciprocal penetration network structure of reactive acrylic diluent within the first body and the second body. Methods that include... [Aspect 8] The method according to embodiment 7, wherein applying an adhesive further comprises applying the adhesive along a circular raised periphery of the posterior element of the intraocular lens, the adhesive being used to bond the posterior element to the anterior element of the intraocular lens. [Aspect 9] The first principal component is, Trifluoroethyl methacrylate and, At least one of butyl acrylate and n-butyl methacrylate, The method according to embodiment 7, comprising at least one of phenylethyl acrylate and phenylethyl methacrylate. [Aspect 10] The method according to embodiment 9, wherein the first main component is a crosslinkable polymer that has not yet been crosslinked, and the crosslinkable polymer is bulky and therefore cannot be moved to either the first body or the second body. [Aspect 11] The method according to embodiment 7, wherein the second main component is a reactive acrylic monomer diluent. [Aspect 12] The method according to embodiment 11, wherein the reactive acrylic monomer diluent is 1-adamantyl methacrylate (ADMA). [Aspect 13] The method according to embodiment 7, wherein the second main component is present in the adhesive in an amount between 18% and 43%. [Aspect 14] The method according to embodiment 7, wherein the adhesive further comprises a photoinitiator. [Aspect 15] The method according to embodiment 14, wherein the photoinitiator is present in the adhesive in an amount of about 2% of the adhesive composition. [Aspect 16] The method according to embodiment 7, wherein the adhesive is cured using UV light. [Aspect 17] A method for purifying silicone oil used in adjustable intraocular lenses, wherein the method is: The process involves fractionating silicone oil using a fractionation process that includes heated isopropyl alcohol and water as reagents, A method comprising evaporating isopropyl alcohol and water from the silicone oil. [Aspect 18] The method according to 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 according to embodiment 17, wherein the average molecular weight of the silicone oil is between 4500 and 6500. [Aspect 20] The method according to embodiment 17, wherein the silicone oil comprises dimethylsiloxane and diphenylsiloxane, and the ratio of dimethylsiloxane to diphenylsiloxane is between 1:1 and 3:1. [Explanation of Symbols]

[0160] 10. Adjustable intraocular lenses 12 Optics Department 14 Support part 18 Front element 20 Rear elements 22 Support fluid chamber 24 Optical Fluid Chamber 26 Opening 28 Peripheral surface 29 Buttress section 32 channels 42 Outer part of the support

Claims

1. A method for refining silicone oil used in accommodative intraocular lenses, The silicone oil is fractionated using a fractionation method that includes high-temperature isopropyl alcohol and water as reagents, A method comprising evaporating isopropyl alcohol and water from the aforementioned silicone oil.

2. The method according to claim 1, wherein the unfractionated silicone oil has a polydispersity index (PDI) greater than 1.

5.

3. The unfractionated silicone oil has a polydispersity index (PDI) of 1.4 to 1.

5. The method according to claim 1.

4. The method according to claim 1, wherein the unfractionated silicone oil has a polydispersity index (PDI) of 1.3 to 1.

4.

5. The method according to claim 1, wherein the unfractionated silicone oil has a polydispersity index (PDI) of 1.2 to 1.

3.

6. The method according to claim 1, wherein the fractionated silicone oil obtained by the fractionation method has a PDI of less than 1.

2.

7. The method according to claim 1, wherein the fractionated silicone oil obtained by the fractionation method has a PDI of 1.1 to 1.

2.

8. The method according to claim 1, wherein the silicone oil comprises 80% dimethylsiloxane and 20% diphenylsiloxane, and the average molecular weight of the silicone oil is 4500 to 6500.

9. The method according to claim 1, wherein the silicone oil has a refractive index that matches that of the polymer material used in the manufacture of the adjustable intraocular lens.

10. Adhesive compound, A first component containing a monomer, An adhesive formulation comprising a second component containing a reactive acrylic monomer diluent, wherein the second component constitutes 23% to 43% of the adhesive formulation.

11. The adhesive compound according to claim 10, wherein the first component is a crosslinkable polymer.

12. The adhesive compound according to claim 10, wherein the monomer comprises butyl acrylate or n-butyl methacrylate, and the butyl acrylate or n-butyl methacrylate constitutes 35% to 45% of the first component.

13. The adhesive compound according to claim 10, wherein the monomer comprises phenylethyl acrylate or phenylethyl methacrylate, and the phenylethyl acrylate or phenylethyl methacrylate constitutes 20% to 40% of the first component.

14. The adhesive compound according to claim 10, wherein the monomer comprises trifluoroethyl methacrylate, and the trifluoroethyl methacrylate constitutes 15% to 30% of the first component.

15. The adhesive compound according to claim 10, wherein the first component constitutes 55% to 75% of the adhesive compound.

16. Adhesive compound, Trifluoroethyl methacrylate and, At least one of butyl acrylate and n-butyl methacrylate, At least one of phenylethyl acrylate and phenylethyl methacrylate, A reactive acrylic monomer diluent is included, The reactive acrylic monomer diluent is present in an amount of 23% to 43% of the adhesive compound. The adhesive formulation wherein the reactive acrylic monomer diluent is 1-adamantyl methacrylate (ADMA).

17. The adhesive formulation according to claim 16, further comprising a UV blocking agent.

18. The adhesive compound according to claim 16, further comprising a photoinitiator.

19. The adhesive formulation according to claim 18, wherein the photoinitiator is 2% of the adhesive formulation.

20. The adhesive compound according to claim 16, wherein the adhesive compound is configured to be cured by UV light.

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