Polymer composition showing a nano-gradient of refractive index

Abstract

To provide methods of producing a precision multi-directional nanogradient of refractive index in a polymeric composition.SOLUTION: There is provided a method of inducing a non-uniform cross-link density in a polymeric material, the method comprising the steps of: providing an already cross-linked three dimensional polymeric matrix comprising a plurality of cross-linkage; and irradiating the already cross-linked three dimensional polymeric matrix with ionization energy to cleave at least a portion of the plurality of cross-linkage to induce a non-uniform cross-link density in the three dimensional polymeric matrix. There is also provided a method comprising disposing the three dimensional polymer matrix in a hydration solution to cause non-uniform swelling of the three dimensional polymer matrix to produce a non-uniform refractive index within the three dimensional polymeric matrix, after the irradiation step.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application is a continuation of U.S. Provisional Patent Application No. 62 / 765,088, filed August 17, 2018. No. 6,313,535, filed on Oct. 13, 2003, and which is incorporated by reference herein for all purposes.

[0002] (Technical field) Ionizing radiation absorbing, dose sensitive and highly flexible polymeric compositions exhibiting multidirectional changes in refractive index Also provided are compositions for producing precise multi-directional gradients of refractive index in polymer compositions. A method is also provided. [Background technology]

[0003] A lens that has a refractive index that varies in a controlled manner throughout the lens body is called a gradient refractive index (G They are called RIN (refraction indices) lenses. The refractive index usually varies gradually throughout the lens body. The naturally occurring human crystalline lens is a lens with a refractive index gradient. Here is one example.

[0004] Transfer of (ultraviolet) light-curable materials with various refractive indices (oligourethane methacrylate) Patent application title: Single foldable multifocal gradient intraocular lens manufactured using stepwise polymerization technique in a mold The fabrication of an IOL has been reported. Malyugin et al., Middle East Asia See fr.J.Ophthalmol.January-March 2014;21(1):32-39 This technique can produce multifocal artificial lenses with gradient optics. The process combines the polymerization step of the material with the production of the lens simultaneously. Summary of the Invention

[0005] By controlling the change in refractive index, it is possible to define optical parameters such as image quality, focal length, and depth of focus for the manufactured lens. Therefore, a methodology for forming a GRIN IOL is desirable. With this methodology, an intraocular lens (e.g., IOL, etc.) can be manufactured according to the specifications of the visual correction requirements of a specific patient. Similar to the methodology for preparing a GRIN lens for applications other than intraocular use, a methodology that enables refractive index correction of a pre-manufactured ophthalmic lens would be desirable. In terms of being able to define optical parameters such as image quality, focal length, and depth of focus for the manufactured lens by controlling the change in refractive index, a methodology for forming a GRIN IOL is desirable. With this methodology, an intraocular lens (e.g., IOL, etc.) can be manufactured according to the specifications of the visual correction requirements of a specific patient. For applications other than intraocular use, a methodology for preparing a GRIN lens is similar. A methodology that enables refractive index correction of a pre-manufactured ophthalmic lens would be desirable. In terms of being able to define optical parameters such as image quality, focal length, and depth of focus for the manufactured lens by controlling the change in refractive index, a methodology for forming a GRIN IOL is desirable. With this methodology, an intraocular lens (e.g., IOL, etc.) can be manufactured according to the specifications of the visual correction requirements of a specific patient.

[0006] One aspect of the present disclosure is a lens including an optical body made from a copolymer having a three-dimensional polymer matrix, optionally an ophthalmic lens, wherein the three-dimensional polymer matrix of the copolymer has a non-uniform crosslink density. The three-dimensional polymer matrix of the copolymer may include a first region with less crosslinking than a second region. The first region and the second region may be within a crosslink density gradient. The three-dimensional polymer matrix may further include a third region not within the gradient, and the third region includes a layer having a uniform crosslink density. The first region may be closer to the periphery of the optical body than the second region.

[0007] The first region may be a first layer having a first crosslink density, and the second region may be a second layer having a second crosslink density. The first region may be a surface layer of the optical body and has less crosslinking than the second region. The first region may be closer to the periphery of the optical body.

[0008] The entire optical body may have a crosslink density gradient. The three-dimensional polymer matrix of the copolymer may include a first region with less crosslinking than a second region. The first region and the second region may be within a crosslink density gradient. The three-dimensional polymer matrix may further include a third region not within the gradient, and the third region includes a layer having a uniform crosslink density. The first region may be closer to the periphery of the optical body than the second region.

[0009] The first region may be a first layer having a first crosslink density, and the second region may be a second layer having a second crosslink density. The first region may be a surface layer of the optical body and has less crosslinking than the second region. The first region may be closer to the periphery of the optical body. The entire optical body may have a crosslink density gradient.

[0010] The first region may be closer to the periphery of the optical body.

[0011] The entire optical body may have a crosslink density gradient.

[0012] The three-dimensional polymer matrix may have a refractive index distribution substantially the same as that of the natural crystalline lens. It may have.

[0013] The shape of the optical body may be substantially the same as that of the natural crystalline lens.

[0014] The entire optical body may not have a crosslink density gradient.

[0015] The optical body may be a toric lens.

[0016] The copolymer may include at least one nonionic acrylic monomer and at least one ionic monomer. The copolymer may further include a collagen material. It may include. The ionic monomer may be an organic acid. The weight ratio of the nonionic acrylic monomer to the ionic monomer is from 10:1 to 10,000:1, for example from 50:1 to 200:1, for example from 75 :1 to 175:1, for example 75:1, 100:1, 125:1, 150:1, or 175 :1. The nonionic acrylic monomer may be hydroxyethyl methacrylate. It may be. It may be.

[0017] The non-uniform crosslink density of the matrix may be adapted to produce an antireflection surface layer on the optical body when the optical body is exposed to the aqueous humor of the eye. The antireflection layer may include a region of the matrix having a thickness of 50 nm to 400 nm. The antireflection layer may include a region of the matrix having a thickness of 0.1 μm to 10 μm. It may include a region of the matrix having a thickness of 50 nm to 400 nm. The antireflection layer may include a region of the matrix having a thickness of 0.1 μm to 10 μm. The antireflection layer may include a region of the matrix having a thickness of 1 μm to 100 μm. The antireflection surface layer may be at least partially disposed around the central opening formed in the optical body. It may include a region of the matrix having a thickness of 0.1 μm to 10 μm. The antireflection layer may include a region of the matrix having a thickness of 1 μm to 100 μm. The antireflection surface layer may be at least partially disposed around the central opening formed in the optical body. It may include a region of the matrix having a thickness of 1 μm to 100 μm. The antireflection surface layer may be at least partially disposed around the central opening formed in the optical body. The antireflection surface layer may be at least partially disposed around the central opening formed in the optical body. It may be.

[0018] The optical body may be the optical body of the IOL.

[0019] The three-dimensional matrix is dimensionally stable against steam sterilization as part of the "wet cloth" and may be hydrolytically stable during long-term use.

[0020] The non-uniform crosslink density may allow the optical body to adapt and converge light from a wide range of distances without moving or changing shape, optionally with a convergence of 0 to 3D, optionally 0 to 2.5D, optionally 0 to 2D, optionally 0 to 1.5D, optionally 0 to 1.0D, when placed in the eye and exposed to aqueous humor. It may converge light from a wide range of distances without moving or changing shape, optionally with a convergence of 0 to 3D, optionally 0 to 2.5D, optionally 0 to 2D, optionally 0 to 1.5D, optionally 0 to 1.0D.

[0021] The non-uniform crosslink density may adapt the optical body to correct astigmatism when placed in the eye and exposed to aqueous humor. It may adapt the optical body to correct astigmatism when placed in the eye and exposed to aqueous humor.

[0022] The three-dimensional polymer matrix may have a lower crosslink density near the surface of the optical body than in the region further inside the surface. It may have a lower crosslink density near the surface of the optical body than in the region further inside the surface.

[0023] The lens may further include a non-optical body part (e.g., one or more haptic parts), and the non-optical body part includes a non-optical three-dimensional polymer matrix having a non-uniform crosslink density. The non-optical body part includes a non-optical three-dimensional polymer matrix having a non-uniform crosslink density. The non-optical three-dimensional polymer matrix has a non-uniform crosslink density.

[0024] The lens may further include a hydration solution to which the optical body is exposed, and the non-uniform crosslink density causes the three-dimensional polymer matrix to swell non-uniformly when hydrated in the solution. This results in a non-uniform refractive index within the optical body. The lens may further include a hydration solution to which the optical body is exposed, and the non-uniform crosslink density causes the three-dimensional polymer matrix to swell non-uniformly when hydrated in the solution. This results in a non-uniform refractive index within the optical body. This results in a non-uniform refractive index within the optical body.

[0025] The hydration solution may be a balanced salt solution.

[0026] The water and solution may include components such that when the lens is exposed to the aqueous humor of the eye, the swelling of the three-dimensional polymer matrix does not substantially change. The hydrating solution may be a balanced salt solution. The hydrating solution may include components such that when the lens is exposed to the aqueous humor of the eye, the swelling of the three-dimensional polymer matrix increases. The hydrating solution may be a sodium chloride solution.

[0027] The water and solution may include components such that when the lens is exposed to the aqueous humor of the eye, the swelling of the three-dimensional polymer matrix increases. The hydrating solution may be a sodium chloride solution. The hydrating solution may include components such that when the lens is exposed to the aqueous humor of the eye, the swelling of the three-dimensional polymer matrix increases. The hydrating solution may be a sodium chloride solution.

[0028] The water and solution may include components such that when the lens is exposed to the aqueous humor of the eye, the swelling of the three-dimensional polymer matrix decreases.

[0029] The hydrating solution may contain at least one of magnesium ions or calcium ions.

[0030] The non-uniform refractive index may include first and second discrete layers each having a first and a second refractive index. The non-uniform crosslink density may further include a crosslink density gradient. The non-uniform crosslink density may further include a crosslink density gradient.

[0031] One aspect of the present disclosure is a method of placing any of the lenses herein in a hydrating solution, which causes non-uniform swelling of the matrix when the lens is placed in the hydrating solution, thereby generating a non-uniform refractive index in the optical body. This method may include placing the lens in a balanced salt solution. Placing the lens in a hydrating solution causes non-uniform swelling of the matrix, thereby generating a non-uniform refractive index in the optical body. This method may include placing the lens in a balanced salt solution. This method may include placing the lens in a balanced salt solution.

[0032] One aspect of the present disclosure is a method of implanting any of the lenses herein, which causes a change in the swelling of the matrix. The implantation may cause further swelling of the matrix in at least a portion of the matrix. The implantation may be such that at least a portion of the matrix swells. The implantation causes a change in the swelling of the matrix. The implantation may cause further swelling of the matrix in at least a portion of the matrix. The implantation may cause further swelling of the matrix in at least a portion of the matrix. ​​​​​It may cause a decrease in moisture. When implanting the lens, the overall volume of the lens may increase with respect to the implanted configuration.

[0033] One aspect of the present disclosure is a method of implanting any of the lenses herein, and this implantation method does not cause a substantial change in the swelling of the matrix.

[0034] One aspect of the present disclosure is a method of implanting any of the lenses herein, and the implantation of the lens includes inserting the lens through a delivery device in a state where the lens has a volume smaller than the lens volume in a fully hydrated implanted state.

[0035] One aspect of the present disclosure is a method of inducing a refractive index gradient in a three-dimensional polymer matrix, the method comprising providing a three-dimensional polymer matrix having a copolymer system prepared from at least one non-ionic acrylic monomer and at least one ionic monomer (e.g., a formed body that has already been cured), and irradiating the three-dimensional polymer matrix with ionization energy in a pattern configured to generate a non-uniform crosslink density within the matrix. rays.

[0036] This method can be used in combination with any of the lenses herein.

[0037] The ionization energy may be an electron beam. The ionization energy may be X-rays.

[0038] This method may further include maintaining the formed body in a stationary position, and the irradiation includes moving the ionization energy source in at least one direction. This method Maintaining the energy source in a stationary position and moving the forming body in at least one direction during the irradiation step may be included. This method may include moving both the forming body and the energy source simultaneously or sequentially or in any combination thereof.

[0039] The irradiation step may generate a crosslink density gradient in at least a portion of the matrix.

[0040] The irradiation step may generate a crosslink density gradient substantially throughout the matrix.

[0041] The irradiation step may generate a first layer having a first crosslink density lower than the crosslink density of a second region of the matrix. The first layer may be the surface layer of the forming body.

[0042] The copolymer system may further include a collagen material.

[0043] The ionic monomer may be an organic acid.

[0044] At least one non-ionic acrylic monomer may be hydroxyethyl methacrylate and at least one ionic monomer may be an acrylic monomer .

[0045] The forming body may be the optical body of an intraocular lens.

[0046] The irradiated three-dimensional polymer matrix may be dimensionally stable with respect to steam sterilization as part of a "wet compress" and hydrolytically stable during long-term use.

[0047] The irradiation step may optionally generate an antireflection surface layer having a thickness of 50 nm to 400 nm, optionally 0.1 μm to 10 μm, or optionally 1 μm to 100 μm. ​​​

[0048] The irradiation step may produce a non-uniform crosslink density, which may result in the former becoming insoluble in the aqueous humor of the eye. When hydrated, the formation body adapts to any shape without moving or changing shape. Wide range of convergence from 0 to 3D, optional 0 to 2.5D, optional 0 to 2D, optional 0 to 1.5D The light may be focused from a distance of

[0049] The irradiating step may be performed such that one or more peripheral supports (e.g., haptics) are integrally formed with the formed body. It can be started after the

[0050] The ionizing energy may be X-rays. [Brief description of the drawings]

[0051]

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DETAILED DESCRIPTION OF THE INVENTION

[0052] One aspect of the present disclosure includes lenses (e.g., ophthalmic lenses) manufactured with a refractive index (「RI」) that varies in a controlled manner throughout the lens body. In some cases, the RI varies only in a part of the lens body. In some cases, the varying RI may be an RI gradient, but in some examples, generally, it may refer to one or more layers of the lens body each having a different RI. The lenses of this specification may include one or more lens body regions having an RI gradient, as well as one or more lens body regions having a uniform RI, and any combination thereof.

[0053] One aspect of the present disclosure is related to a method for generating a varying RI within a lens.​​​

[0054] Generally, the method of generating a variable RI in a lens body (referred to herein as an optical body) is performed after the lens body of the material is formed, i.e., after curing one or more monomers to form a cured body of the polymer material. This is in contrast to alternative approaches that may generate various RIs during the process of forming the lens body.

[0055] The method herein of generating various RIs may be performed after one or more optical surfaces have already been formed in the optical body (e.g., via turning to generate one or more optical surfaces). Or, the method of generating various RIs may be performed before forming one or more optical surfaces of the optical body. For example, the method may be performed before the front and / or rear surfaces of the optical body are formed (e.g., by turning). In these alternatives, the method may be performed, for example, on a cured body of polymer material (e.g., a cylindrical button), and then one or more optical surfaces may be formed thereon.

[0056] An exemplary advantage of the method described herein is that it can be used on a wide variety of optical bodies formed using known curing techniques. This allows for forming an optical body of a material (e.g., cured) using existing techniques, and then using the method herein to change the RI of one or more regions of the lens in a very controlled manner to address a wide variety of optical impairments (e.g., astigmatism), or otherwise modify the lens to produce a desired optical effect (e.g., generate an anti-reflective surface layer in the outermost region of the lens).

[0057] The term "refractive index" ("RI") as used herein encompasses the measurement of the refractive index in a translucent / transparent material, particularly in the eye media. RI is measured as the relative speed of light in another medium (e.g ., a polymeric material) compared to the speed of light in a vacuum. For example, the RI (n) of water is 1.33.

[0058] Any of the lenses herein may have one or more regions having an RI gradient . Any of the lenses herein may have one or more regions that interface at locations where the RI changes abruptly between regions . Any of the lenses herein may have one or more regions having a constant RI . Any of the lenses herein may include any combination of the exemplary regions described in this paragraph. Any of the lenses described in this paragraph may be created using any of the methods used herein .

[0059] The natural human crystalline lens is a gradient refractive index (GRIN) lens, and the RI varies as a gradient in that it typically changes gradually across the entire body of the lens . As an example, the methods herein can facilitate the manufacture of a lens having performance similar to that of the eye's crystalline lens by defining optical parameters such as image quality, focal length, and depth of focus by controlling the change in refractive index, and the manufactured lens is a GRIN lens. However, for some lenses, it may be advantageous to provide an artificial lens having one or more abrupt changes in RI instead of, or in addition to, a gradient . Portions of the lens may also have a constant RI .

[0060] The disclosure herein provides a method of generating a desired RI profile within an already formed lens ​​​​includes a method. The technology herein applies ionization energy to a formed polymer material in a specific pattern or method, and in some cases, the ionization energy may be an electron beam. The bonds of the formed polymer material are broken by the electron beam (or other ionization energy). Subsequently, when the polymer material is hydrated with a solution (e.g., balanced salt solution ("BSS") or other solvent (e.g., water)), the polymer material swells. The swelling of the polymer material causes a decrease in RI. In this way, the applied energy can be used to change the RI within the lens in a controlled and predictable manner to generate a desired RI profile for the lens. Ionization energy is applied, and in some cases, the ionization energy may be an electron beam. The bonds of the formed polymer material are broken by the electron beam (or other ionization energy). Subsequently, when the polymer material is hydrated with a solution (e.g., balanced salt solution ("BSS") ) or other solvent (e.g., water), the polymer material swells. The swelling of the polymer material causes a decrease in RI. In this way, the applied energy can be used to change the RI within the lens in a controlled and predictable manner to generate a desired RI profile for the lens.

[0061] To form the polymer body, crosslinking is first performed. This may be referred to herein as "curing" and can be carried out using known techniques. In some embodiments, the first and second components are crosslinked to produce a three-dimensional structure random copolymer. Chemical crosslinking can be carried out using a combination of initiators and / or crosslinking agents and / or catalysts. Alternatively, crosslinking can be initiated using Compton electrons indirectly generated by a nuclear irradiation device. For example, cesium 137 or cobalt 60 sources that provide gamma rays that penetrate the lens material, ionize the material, and generate Compton electrons (i.e., electrons separated during ionization) can be used. Both chemical crosslinking methods and nuclear irradiation agent crosslinking methods provide an environment that results in a uniform crosslinking rate within the reaction region, and thus a homogeneous polymer can be produced. The copolymer can take the form of a tangled coil in BSS instead of being linear.

[0062] Instead of being linear, the copolymer can take the form of a tangled coil in BSS. 。A random three-dimensional cross-linked coil is formed only when the intermolecular force between the copolymer and the solvent molecules is equal to the force between the solvent molecules and also equal to the force between the copolymer chain segments. A random three-dimensional cross-linked coil is formed during the polymerization / cross-linking process when a destruction process occurs during the final gelation equilibrium point and the construction rate and the destruction rate become equal. Again, this can be possible by either a chemical cross-linking or a radiation process. In the chemical cross-linking process, the combination of an initiator and / or a cross-linking agent and / or a catalyst that promotes cross-linking coincides with the action of an inhibitor. In the radiation process, when the cross-linking density reaches a critical level, cross-linking and bond cleavage begin to occur at the same rate. After the polymer body is formed, ionization energy is applied to the polymer body, resulting in the destruction of the cross-linking bonds. FIG. 1 conceptually shows a system 10 including an ionization energy source 12, ionization energy 14, and a polymer body 15 formed (cured) thereon. The polymer body 15 may or may not have an optical surface formed thereon. The polymer body 15 is stably attached and may be irradiated using ionization energy 14. When the electron beam is the ionization energy, the electron beam technology used in electron beam lithography for semiconductor manufacturing can be easily applied to the method of the embodiments herein. With electron beam technology, custom patterns can be drawn (directly written) with a resolution of less than 10 nm. For example, see Altissimo, M., E-beam lithography for micro- / nanofabrication B iomicrofluidics 4, 026503 (2010). Deflection plate 1 。 。 。 。 。

[0063] 。 。 。 。 。 。 。 。 。 lithography for micro- / nanofabrication B iomicrofluidics 4, 026503 (2010). Deflection plate 1 3 is also shown and is used to generate a potential for deflecting the beam onto the polymer body 15. .

[0064] Various system configurations are conceivable. For example, a static lens may be provided, and an electron beam that can move relative to the static lens to generate an irradiation pattern may be provided. Alternatively, a stationary source may be used, and the polymer body may be applied so as to move in any degree of freedom shown as the arrow in FIG. 1. Alternatively, both the stationary source and the lens may be moved. . Or, a stationary source may be used, and the polymer body may be applied so as to move in any degree of freedom shown as the arrow in FIG. 1. Alternatively, both the stationary source and the lens may be moved. . Or, a stationary source may be used, and the polymer body may be applied so as to move in any degree of freedom shown as the arrow in FIG. 1. Alternatively, both the stationary source and the lens may be moved. . Or, a stationary source may be used, and the polymer body may be applied so as to move in any degree of freedom shown as the arrow in FIG. 1. Alternatively, both the stationary source and the lens may be moved.

[0065] The irradiation pattern is defined by the electron energy, the direction and position at which the electrons hit the lens, and the time during which any position in space is irradiated. Conversely, a lens suitable for movement (e.g., in six degrees of freedom as shown in FIG. 1) may be provided that is placed in the path of the static electron beam and moves in response to the beam to generate an irradiation pattern. A configuration in which both the lens and the electron beam are moved may also be employed. . Conversely, a lens suitable for movement (e.g., in six degrees of freedom as shown in FIG. 1) may be provided that is placed in the path of the static electron beam and moves in response to the beam to generate an irradiation pattern. A configuration in which both the lens and the electron beam are moved may also be employed. . Conversely, a lens suitable for movement (e.g., in six degrees of freedom as shown in FIG. 1) may be provided that is placed in the path of the static electron beam and moves in response to the beam to generate an irradiation pattern. A configuration in which both the lens and the electron beam are moved may also be employed. . Conversely, a lens suitable for movement (e.g., in six degrees of freedom as shown in FIG. 1) may be provided that is placed in the path of the static electron beam and moves in response to the beam to generate an irradiation pattern. A configuration in which both the lens and the electron beam are moved may also be employed. . Conversely, a lens suitable for movement (e.g., in six degrees of freedom as shown in FIG. 1) may be provided that is placed in the path of the static electron beam and moves in response to the beam to generate an irradiation pattern. A configuration in which both the lens and the electron beam are moved may also be employed.

[0066] An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity . An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity . An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity . An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity . An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity . An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity . An exemplary manner of a method that can be modified to control the resulting RI profile of the lens is the angle of incidence of the electrons. In a particular embodiment, it is desirable for the electrons to hit the lens at an angle of view (e.g., over the entire surface of the lens). This enables, for example, the more advantageous use of higher energies when preparing the surface layer. This may be regarded as controlling the amount of absorbed energy or the intensity of the electron beam by controlling the angle of incidence. FIG. 2 shows this concept, showing that the lens 20 and the energy 22 are hitting the lens at an angle of view (shallow). The lens 20 is an energy source (here for simplicity It may move relative to (as shown for) the lens, and the energy source may move relative to the lens or relative to both the lens and the energy source. It may move relative to both the lens and the energy source.

[0067] The application of ionization energy (e.g., an electron beam) is different from the above-described irradiator for crosslinking (for polymer body formation) in that the ionization energy in this step is directed in a specific pattern across the entire lens. When the beam interacts with the polymer material, the bonds in the polymer backbone are broken, and when placed in a solution (BSS, aqueous humor, etc.), the polymer body swells and the refractive index changes. The resulting combination of selected parameters can produce a GRIN in a material that can withstand steam sterilization (if there is water in the material). Radiation with different absorbed doses has an effect that is directly proportional to the swelling index, and the resulting effect on the polymer system provides a mechanism for forming a GRIN. When the beam interacts with the polymer material, the bonds in the polymer backbone are broken, and when placed in a solution (BSS, aqueous humor, etc.), the polymer body swells and the refractive index changes. When the beam interacts with the polymer material, the bonds in the polymer backbone are broken, and when placed in a solution (BSS, aqueous humor, etc.), the polymer body swells and the refractive index changes. When the beam interacts with the polymer material, the bonds in the polymer backbone are broken, and when placed in a solution (BSS, aqueous humor, etc.), the polymer body swells and the refractive index changes. When placed in a solution (BSS, aqueous humor, etc.), the polymer body swells and the refractive index changes. The resulting combination of selected parameters can produce a GRIN in a material that can withstand steam sterilization (if there is water in the material). When placed in a solution (BSS, aqueous humor, etc.), the polymer body swells and the refractive index changes. The resulting combination of selected parameters can produce a GRIN in a material that can withstand steam sterilization (if there is water in the material). Radiation with different absorbed doses has an effect that is directly proportional to the swelling index, and the resulting effect on the polymer system provides a mechanism for forming a GRIN. Radiation with different absorbed doses has an effect that is directly proportional to the swelling index, and the resulting effect on the polymer system provides a mechanism for forming a GRIN.

[0068] Figures 3A, 3B, 4A, and 4B generally show how the application of ionization energy to a polymer material can increase the amount of swelling when hydrated, resulting in a greater decrease in the RI. Figures 3A, 3B, 4A, and 4B generally show how the application of ionization energy to a polymer material can increase the amount of swelling when hydrated, resulting in a greater decrease in the RI. Figure 3A shows a formed polymer material having crosslinks 30 (only three are labeled) generally shown as a square. This is said to be in a "dry" state. Figure 3A shows a formed polymer material having crosslinks 30 (only three are labeled) generally shown as a square. This is said to be in a "dry" state. Figure 3B shows the polymer material when hydrated with a solution (e.g., BSS, magnesium, calcium, etc.). In Figure 3B, the polymer material is swollen compared to the dry state of Figure 3A. The positive charges 32 (only three are labeled for clarity) neutralize each other. The positive charges 32 (only three are labeled for clarity) neutralize each other.

[0069] Figure 4A shows the polymer material after exposure to ionization energy 40. As shown , some crosslinks 42 have been broken by exposure to ionization energy 41 . Similar to Figure 3A, Figure 4A can be referred to as the dry state of the polymer material

[0070] Figure 4B shows the polymer hydrated with a solution (e.g., BSS, magnesium, calcium, etc.) . As can be seen by comparing Figures 3B and 4B, the polymer material (exposed to at least ionization energy) swells significantly after ionization energy absorption compared to when it is not exposed to ionization energy

[0071] Figure 5 shows in more detail how swelling occurs. In the case of an IOL, the optical properties of the lens when the lens is placed in the eye become a problem. The copolymer increases swelling in solution in the presence of calcium and magnesium cations. Due to diffusion from the solution (e.g., aqueous humor) in which the lens is placed, Ca and Mg ions are present within the material, so the variation in swelling within the lens can be controlled. The greater the swelling, the more water there is in the matrix, resulting in a lower refractive index. Figure 5 shows the chemical process related to polymethyl methacrylate (PMMA) and can be modified for use with acrylates 2+ and Mg 2+ ions are present within the material

[0072] At the top left of Figure 5, a pair of hydrogen bonds are shown between two methacrylate groups to indicate weak crosslinks . In the presence of Ca 2+ and Mg 2+ ions, the cations bind to the oxygen atoms at the ends of the methacrylate groups, generating bundles of four or more weakly bonded units ​​​​​​​Stronger complexes may be formed. These species are hydrophilic and therefore have a higher affinity for the matrix. The high energy electrons attract water into the polymer, causing it to swell and lowering its refractive index. When the light enters the polymer backbone, the bonds in the polymer backbone are broken, and according to the Flory-Huggins solution theory, Additional swelling may occur, resulting in a further decrease in the refractive index. Polymerization of Ca 2+ and Mg 2+ A hydrophilic polymer is produced that swells in the presence of ions. When irradiated with an electron beam (an example is shown in Figure 4A), the bonds in this synthetic polymer chain are This technique can be used in conjunction with the techniques described herein (e.g., The method may be used in any of the above methods (to produce an antireflection layer).

[0073] The lenses herein, after crosslinking, are generally referred to as being in a dry state. When placed in aqueous humor (SS, aqueous humor of the eye), the polymeric material swells compared to its dry state. The amount of swelling is Depending on the solution in which the lens is placed, the lens is generally The device is packaged for implantation in the eye when ready for use. The lenses are exposed to BS (which has been exposed to cause some swelling of the dry polymeric material). S., and when implanted, they are exposed to aqueous humor, causing slight additional swelling. This may happen.

[0074] Any of the lenses herein are designed so that the lens does not undergo substantial additional swelling after implantation. This allows the lens to be as close to its final size as possible at the time of implantation. For example, the lens may be able to function properly immediately after implantation. It may be desirable to implant in a "full" size for stability.

[0075] Or, it may be desirable to implant the lens in a size smaller than its final fully implanted size (i.e., less swelling ). For example, the implanted lens may be smaller to facilitate advancement through the delivery tool and then expand to a larger size up to the final implanted size . In this way, the degree of swelling after implantation can be controlled as needed based on the application.

[0076] Using the general method of the specification to generate a refractive index gradient profile in at least a portion of the lens, the lens can be customized for an individual patient.

[0077] This approach offers a wide variety of possibilities in that it can meet the requirements of many patients by using the techniques of this specification. A particular patient may benefit from a particular RI profile file of the lens. The techniques of this specification can be adjusted as needed to generate a particular RI profile in the lens. These and other characteristics can be provided using the methods of the embodiments, in contrast to a single refractive index material where the optical characteristics are determined only by the form of the lens. The electron beam can be advantageously used for surface or bulk modification, and other energies such as ionizing radiation from a radiation source such as X-rays, leptons, protons, positrons, or an α or β source can also be used. There are a wide variety of specific applications for the general methods described herein. Some specific ones will be described below. The general methods described herein can be used to provide lenses with a wide variety of optical characteristics that are not limited to those determined solely by the form of the lens.

[0078] The electron beam can be advantageously used for surface or bulk modification, and other energies such as ionizing radiation from a radiation source such as X-rays, leptons, protons, positrons, or an α or β source can also be used. For example, the electron beam can be used to generate a refractive index gradient profile in at least a portion of the lens to customize the lens for an individual patient. This approach can meet the requirements of many patients by using the techniques of this specification.

[0079] There are a wide variety of specific applications for the general methods described herein. Some specific Examples are provided herein, but the general method can be used for other applications to generate a desired RI profile for a variety of lenses. It is understood that a desired RI profile can be generated for a variety of lenses.

[0080] One aspect of the present disclosure is a manufacturing method for manufacturing lenses such as intraocular lenses (e.g., IOLs, artificial substitutes for the eye's crystalline lens), having a refractive index gradient (GRIN) that can be controlled in a large number of ways that vary in size and continuously. The GRIN lens has a multi-directional gradient of refractive index that can be controlled in a large number of ways that vary in size and continuously. The material of the GRIN lens is dimensionally stable with respect to steam sterilization as part of a "wet pack" and is hydrolytically stable even with long-term use. The GRIN lens is due to the material of the lens and has a narrow three-dimensional crosslinked distribution, so it does not change even with long-term use. With these manufacturing methods, the lens can be designed to solve many problems. For example, but not limited to, an exemplary use of these methods is to create an anti-reflection layer within the lens by creating a thin layer of material with a reduced refractive index. Figure 6 shows an exemplary lens 50 having a thin anti-reflection layer 52 formed therein and a main lens body portion 54.

[0081] For example, but not limited to, an exemplary use of these methods is to create an anti-reflection layer within the lens by creating a thin layer of material with a reduced refractive index. Figure 6 shows an exemplary lens 50 having a thin anti-reflection layer 52 formed therein and a main lens body portion 54. The anti-reflection layer (i.e., the surface layer) reduces stray light within the eye that can cause visual impairment and is useful in reducing unwanted reflections in lens applications other than IOLs. For example, but not limited to, an exemplary use of these methods is to create an anti-reflection layer within the lens by creating a thin layer of material with a reduced refractive index.

[0082] The anti-reflection layer (i.e., the surface layer) reduces stray light within the eye that can cause visual impairment and is useful in reducing unwanted reflections in lens applications other than IOLs. In addition, the anti-reflection layer (i.e., the surface layer) reduces unwanted reflections in lens applications other than IOLs and is useful in reducing stray light within the eye that can cause visual impairment. There are situations where it is useful.

[0083] Figures 13A and 13B show an additional exemplary lens 100 including an optical body 102 and a peripheral support 104. The optical body 102 includes an opening 106 (a central opening in this embodiment) extending through the optical body 102. Figure 13B shows irradiated using the method of the present specification. It shows the region 108 of the optical body that forms an opening for generating an antireflection layer at the position of the opening. This may help reduce the scattering of light at the position of the opening.

[0084] The manufacturing process described herein can be operated to form an antireflection layer. Generally , electrons having low energy (e.g., from 500 eV to 10 keV) and optionally high flux (high flux of electrons passing through the surface) can be used for surface modification of the lens. For example, the antireflection layer can be generated, for example, by breaking chemical bonds at the surface, thereby reducing the RI and / or reflectivity. For generating the antireflection layer, electrons in the range of 0.5 keV to 2 keV can be used, and the absorbed radiation dose is in the range of 4 to 8 Mrad. The dose can be higher or lower as well and can also depend on the composition of the irradiated substrate chemical. Or, electrons having an energy of about 0.3 to 1 keV can be used at high flux. When the absorbed dose reaches about 8 Mrad,

[0085] the change in refractive index due to the irradiation depth becomes substantially uniform, and a layer (e.g., layer 52) having substantially the same refractive index with a 75% relative decrease is generated. By appropriately selecting the energy and dose of the electrons, an interference antireflection layer can be generated in the lens material. the thickness of the modified surface layer is mainly affected by the electron energy. This is shown in FIG. 7 and is calculated according to the theoretical formula obtained from Microprobe Analysis, edited by Anderson, C.A., 1973, John Wiley & Sons, 571 pp. By appropriately selecting the energy and dose of the electrons, an interference antireflection layer can be generated in the lens material.

[0086] The thickness of the modified surface layer is mainly affected by the electron energy. This is shown in FIG. 7 and is calculated according to the theoretical formula obtained from Microprobe Analysis, edited by Anderson, C.A., 1973, John Wiley & Sons, 571 pp. It is shown in FIG. 7 and is calculated according to the theoretical formula obtained from Microprobe Analysis, edited by Anderson, C.A., 1973, John Wiley & Sons, 571 pp. ysis, John Wiley & Sons, 571 pp. It is calculated.

Equation

[0087] When the change in refractive index is a step, the desired thickness is one-fourth of the wavelength of light in the modified surface layer and decreases from the wavelength in air by a factor equal to RI. Thus, the thickness of the layer is about 100 - 200 nm. Using a single electron energy, the actual RI change is an exponential decay. Thus, in some embodiments, the thickness is about 100 - 200 nm, for example, may be somewhat smaller or larger than about 50 - 400 nm, and here, the thickness is defined as 1 / e of the maximum RI change. In some embodiments, the thickness is 0.1 μm - 10 μm. In some embodiments, the thickness is 1 μm - 10 μm. By varying the electron energy during exposure, a more stepped layer can be produced. Further more, by varying the thickness of the surface layer as a function of the distance from the center of the lens, the angle of incidence of light on the lens surface can be taken into account. can be taken into account.

[0088] Although the disclosure herein mainly describes an electron beam as the ionization energy, other types of ionization energy such as beta radiation may be used. However, beta rays usually have a higher energy (e.g., 546 keV for 90 Sr → 90 Y), and its use may be limited by the desired thickness of the layer or, in the case of applications other than the antireflection layer, by the thickness of the lens itself. For an IOL, this thickness is between 0.05 mm and 5 mm. Also, the energy of beta rays cannot be adjusted as is the case with electron beams. The electron emission graph shown in FIG. 7 Compared to the rough, Figure 8 shows a relatively high energy range of beta radiation.

[0089] An additional exemplary use is to create a lens that focuses light from a wide range of distances without moving or changing the shape, such that light incident on the lens from various directions and at various surface locations of the lens experiences different optical paths through the lens due to the RI variation across the lens. Since IOLs typically do not provide the same accommodation as provided by the natural lens, focusing light from a wide range of distances is useful to the patient wearing the lens. Further, this technology can be useful in other lens applications, such as camera lenses designed with a large depth of field. The change in refractive index of the surface lens material relative to the bulk lens material depends on the absorbed radiation dose. Figure 9 shows the rate of change of refractive index, where 100% refers to the surface RI that has not changed from the bulk, and 0% refers to the RI being reduced to that of a solution (e.g., balanced salt solution within the package, aqueous humor of the eye, etc.) where the surface RI is retained. Another exemplary use of the general techniques described herein is to create a surface layer that extends over several wavelengths of thickness and does not cause destructive interference of light reflected from both surfaces. This can be represented in Figure 6, where region 52 has a RI gradient rather than being a layer with a uniform RI. In this exemplary method, the RI of the outer surface of the material is reduced to match as closely as possible (e.g., within 10% variance, e.g., within 5% variance) the RI of the aqueous humor. The slight change in RI between the lens and the aqueous humor results in less reflection. According to Fresnel's equation, it is as follows.

[0090] The change in refractive index of the surface lens material relative to the bulk lens material depends on the absorbed radiation dose. Figure 9 shows the rate of change of refractive index, where 100% refers to the surface RI that has not changed from the bulk, and 0% refers to the RI being reduced to that of a solution (e.g., balanced salt solution within the package, aqueous humor of the eye, etc.) where the surface RI is retained.

[0091] Another exemplary use of the general techniques described herein is to create a surface layer that extends over several wavelengths of thickness and does not cause destructive interference of light reflected from both surfaces. This can be represented in Figure 6, where region 52 has a RI gradient rather than being a layer with a uniform RI. In this exemplary method, the RI of the outer surface of the material is reduced to match as closely as possible (e.g., within 10% variance, e.g., within 5% variance) the RI of the aqueous humor. The slight change in RI between the lens and the aqueous humor results in less reflection. According to Fresnel's equation, it is as follows. The RI of the outer surface of the material is reduced to match as closely as possible (e.g., within 10% variance, e.g., within 5% variance) the RI of the aqueous humor. The slight change in RI between the lens and the aqueous humor results in less reflection. According to Fresnel's equation, it is as follows. According to Fresnel's equation, it is as follows.

number

[0092] Multiple directional incidence angles of illumination can be used to illuminate the bulk of the lens, the surface of the lens, or both. In this way, three-dimensional (3D) patterns with different refractive index gradients can be generated. Regardless of the amount of radiation, the effect is determined by the electron energy (penetration) and absorbed dose (magnitude of effect). Therefore, various patterns can be achieved by changing the orientation of the lens beam. For every position in the 3D matrix, the direction of the electron beam and the absorbed dose at that position The depth of the position within the lens relative to is calculated and is then calculated over time as the beam moves This can be done by integrating.

[0093] The above methodology is particularly useful in the surface modification of lenses, examples of which are described herein. However, it is desirable to change the bulk of the lens (i.e., not just the surface). When the electrons are injected into the plasma, high energy (e.g., 10 keV to 700 keV) electrons are used. Therefore, the energy of the beam can be adjusted to a certain extent depending on the application. It can be changed as needed to penetrate to the required depth for the purpose. The energy profile of electrons By adjusting the file and flux, and the incident angle and irradiation position, any part of the lens Overall, a desired RI profile can be realized.

[0094] Generally, a retinal image similar to that provided by the natural lens is such that the brain is accustomed to such an image and the neural network of the brain may be able to process such an image better. Therefore, it may be advantageous for lens recipients. Additional exemplary uses of the methods herein are to create lenses that generate images more similar to those produced by the natural lens. FIG. 10 shows an exemplary lens 60 that can be generated using the methods herein. Lens 60 is made to function like a natural lens and the RI gradually changes, as shown by the internal lines representing the contour lines of the refractive index in FIG. 10. Lens 60 may be implanted in the lens capsule and replace the removed natural lens. In FIG. 10, the front part is towards the bottom of the page and the rear part is towards the top of the page. The RI changes in the lens body, and the RI is greater in the central region 62 than in the outer region 64. Lens 60 is an example of an optical body having a three-dimensional polymer matrix with a refractive index distribution substantially the same as that of the natural lens. Lens 60 is also an example of an optical body having a shape substantially the same as that of the natural lens. Those skilled in the art will understand what is meant by a refractive index distribution substantially the same as that of the natural lens and a shape substantially the same as that of the natural lens. Therefore, those skilled in the art will understand that the comparison with the natural lens (which may be the subject of variations in the object) does not make this description unclear or ambiguous.

[0095] The lens 60 of FIG. 10 is an example of a lens that can be adapted to swell to a final implanted state (size) after implantation. For example, the lens 60 has a smaller delivery size to facilitate delivery via an instrument for inserting the lens, and then, when inserted, it is desirable for it to swell (expand) to a larger state and be better fixed within the eye (e.g., within the lens capsule). For example, the lens 60 has a smaller delivery size to facilitate delivery via an instrument for inserting the lens, and then, when inserted, it is desirable for it to swell (expand) to a larger state and be better fixed within the eye (e.g., within the lens capsule). For example, the lens 60 has a smaller delivery size to facilitate delivery via an instrument for inserting the lens, and then, when inserted, it is desirable for it to swell (expand) to a larger state and be better fixed within the eye (e.g., within the lens capsule). For example, the lens 60 has a smaller delivery size to facilitate delivery via an instrument for inserting the lens, and then, when inserted, it is desirable for it to swell (expand) to a larger state and be better fixed within the eye (e.g., within the lens capsule). For example, the lens 60 has a smaller delivery size to facilitate delivery via an instrument for inserting the lens, and then, when inserted, it is desirable for it to swell (expand) to a larger state and be better fixed within the eye (e.g., within the lens capsule).

[0096] FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree. FIG. 11 shows an alternative optical body 70 having various RIs within the optics that can be generated using the methods herein. The optical body 70 can be incorporated into any suitable ophthalmic lens (e.g., an IOL with one or more haptics). The optical body 70 can be generated by applying ionization energy to a polymer body. Region 74 may be considered a region of lower RI compared to region 72. The RI may vary continuously (gradually) through the lens 70. The lens 70 is an example of a lens configured to treat refractive anomalies (via the spherical component of the lens shape) and astigmatism (via the cylindrical component of the lens shape). The degree of RI change between regions 72 and 74 can be any suitable degree.

[0097] A further embodiment of the methods described herein is to create a Fresnel lens embedded within a lens of a conventional shape, such as a biconvex lens or a biconcave lens. To create the optical power, it is necessary to curve the surface of the lens. In the case of a biconvex lens, it must have a central thickness that increases with the optical power, and in the case of a biconcave lens, it must have an edge thickness that increases with the optical power. The Fresnel lens is curved. A further embodiment of the methods described herein is to create a Fresnel lens embedded within a lens of a conventional shape, such as a biconvex lens or a biconcave lens. To create the optical power, it is necessary to curve the surface of the lens. In the case of a biconvex lens, it must have a central thickness that increases with the optical power, and in the case of a biconcave lens, it must have an edge thickness that increases with the optical power. The Fresnel lens is curved. A further embodiment of the methods described herein is to create a Fresnel lens embedded within a lens of a conventional shape, such as a biconvex lens or a biconcave lens. To create the optical power, it is necessary to curve the surface of the lens. In the case of a biconvex lens, it must have a central thickness that increases with the optical power, and in the case of a biconcave lens, it must have an edge thickness that increases with the optical power. The Fresnel lens is curved. A further embodiment of the methods described herein is to create a Fresnel lens embedded within a lens of a conventional shape, such as a biconvex lens or a biconcave lens. To create the optical power, it is necessary to curve the surface of the lens. In the case of a biconvex lens, it must have a central thickness that increases with the optical power, and in the case of a biconcave lens, it must have an edge thickness that increases with the optical power. The Fresnel lens is curved. A further embodiment of the methods described herein is to create a Fresnel lens embedded within a lens of a conventional shape, such as a biconvex lens or a biconcave lens. To create the optical power, it is necessary to curve the surface of the lens. In the case of a biconvex lens, it must have a central thickness that increases with the optical power, and in the case of a biconcave lens, it must have an edge thickness that increases with the optical power. The Fresnel lens is curved. The lens has a shape that divides the optical efficiency into various sectors, which reduces the thickness of the lens. One drawback of lens is that their curvature can change suddenly, which can scatter light. By fabricating a Fresnel lens within the lens, part of the power is directed outside the conventional lens. By creating a curved zone with increased power, which can be obtained from the shape of the lens, More power can be obtained by replicating the Fresnel lens. The lens may be designed to provide multiple focal points simultaneously, e.g., at long and short distances. It provides good focus at long, short and intermediate distances. The interaction between the different refractive zones of the lens can produce beneficial diffractive effects. Controlling the precise shape of the aperture can reduce scattering and produce better images.

[0098] One aspect of the present disclosure is a copolymer material that can be used to make a GRIN lens. The IO lens may be incorporated into an IOL, for example. L Material properties include high elasticity for easy insertion into the eye, low reflectivity to avoid vision impairment rate, good biocompatibility (e.g., no leaching of toxic substances into the eye), and compatibility with the existing anatomy of the eye. The stable shape of the lens and support elements is mechanically created without disturbance or irritation. This includes being able to be accurately held in place.

[0099] Some ophthalmic devices extend radially outward from the optic and are positioned on the eye. One or more peripheral supports (e.g., plate haptics or arms) that provide support to the optic when Any of the irradiation methods herein may include one or more haptics, such as haptics. The optical body and any peripheral support may be formed in an integral structure (e.g., via a lathe, molding, machining, or any combination thereof) after formation. It may also occur.

[0100] In addition, the method of generating a non-uniform crosslink density described herein may be used in the non-optical part of the lens (e.g., one or more tactile parts). Also, at least a part of the non-optical part may be irradiated to generate a changing refractive index. This is because the size of the pupil is large, so there is a lot of light passing through the non-optical part, which may be useful for reducing light scattering in some subjects with relatively large pupils. Therefore, all the methods of irradiation and swelling described herein may be used in the non-optical part of the lens and the optical body.

[0101] (Exemplary method for preparing refractive index gradient in a three-dimensional copolymer) The copolymer system of a particular embodiment is composed of mostly non-ionic acrylic monomers and a small portion of ionic monomers such as organic acids. The term "organic acid" encompasses acids composed of molecules containing an organic radical (carbon (hydrocarbon)-containing moiety). Such acids include, for example, acrylic acid, formic acid (H-COOH), acetic acid (CH3COOH), and citric acid (C6H8O7), each containing an ionizable -COOH group. The term "acrylic" as applied to the monomers encompasses synthetic plastic resins derived from acrylic acid. Hydrophilic monomers and hydrophobic monomers must be selected such that the hydrophobic monomers are miscible with the hydrophilic monomers. The hydrophilic monomers function as solvents for the hydrophobic monomers. Suitable monomers can be readily selected by those skilled in the art to which the present disclosure pertains. ​​​​​​Examples of suitable acrylic monomers include 4-methacryloxy-2-hydroxybenzophenone, ethyl-3-benzoylacrylate, N-propylmethacrylate (acrylic), ethylmethacrylate, methylmethacrylate, n-hexylmethacrylate, 2-hydroxyethylmethacrylate (HEMA), hydroxypropylmethacrylate, 2-hydroxyethylmethacrylate, hydroxypropylmethacrylate poly(ethylene glycol) n monomethacrylate, 4-hydroxybutylmethacrylate, and other monomers known in the art. When sodium chloride or other salts are present in the copolymer system, it is generally observed that the swelling in water decreases. Therefore, by manipulating the salt content in the copolymer system when the lens is outside the eye, the target swelling amount can be changed. The lens can be expanded more or less when implanted into the eye when exposed to aqueous humor in response to the solution placed before implantation. none, ethyl-3-benzoylacrylate, N-propylmethacrylate) N-propyl methacrylate (acrylic), ethylmethacrylate, methylmethacrylate, n-he xylmethacrylate, 2-hydroxyethylmethacrylate (HEMA), hydroxy propylmethacrylate, 2-hydroxyethylmethacrylate, hydroxypropylmethacrylate poly(ethylene glycol) n monomethacrylate, 4-hydroxybutyl methacrylate, and other monomers known in the art. When sodium chloride or other salts are present in the copolymer system, it is generally observed that the swelling in water decreases. Therefore, by manipulating the salt content in the copolymer system when the lens is outside the eye, the target swelling amount can be changed. The lens can be expanded more or less when implanted into the eye when exposed to aqueous humor in response to the solution placed before implantation. (Refractive Index Gradient of Three-Dimensional Collagen-Containing Copolymer) The copolymer can be modified by adding collagen or similar biomolecules to the polymer, in which case radiation methods can be used. This formulation method provides the structural and dimensional properties of the resulting material that can produce an IOL with GRIN. Any type of collagen from any source can be used. Suitable collagen materials include collagen obtained from the sclera or cornea of porcine eyes, or fibroblasts (e.g., artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, When exposed to aqueous humor in response to the solution placed before implantation, the lens can be expanded more or less when implanted into the eye.

[0102] (Refractive Index Gradient of Three-Dimensional Collagen-Containing Copolymer) The copolymer can be modified by adding collagen or similar biomolecules to the polymer, in which case radiation methods can be used. This formulation method provides the structural and dimensional properties of the resulting material that can produce an IOL with GRIN. Any type of collagen from any source can be used. Suitable collagen materials include collagen obtained from the sclera or cornea of porcine eyes, or fibroblasts (e.g., artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, The copolymer can be modified by adding collagen or similar biomolecules to the polymer, in which case radiation methods can be used. This formulation method provides the structural and dimensional properties of the resulting material that can produce an IOL with GRIN. Any type of collagen from any source can be used. Suitable collagen materials include collagen obtained from the sclera or cornea of porcine eyes, or fibroblasts (e.g., artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, The copolymer can be modified by adding collagen or similar biomolecules to the polymer, in which case radiation methods can be used. This formulation method provides the structural and dimensional properties of the resulting material that can produce an IOL with GRIN. Any type of collagen from any source can be used. Suitable collagen materials include collagen obtained from the sclera or cornea of porcine eyes, or fibroblasts (e.g., artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, Any type of collagen from any source can be used. Suitable collagen materials include collagen obtained from the sclera or cornea of porcine eyes, or fibroblasts (e.g., artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, collagen obtained from the sclera or cornea of porcine eyes, or fibroblasts (e.g., artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, artificially produced or cultured from genetically engineered yeast, etc.), but are not limited thereto. Collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, collagen is a naturally stable polyene containing hydrophobic, hydroxyl, and polar amino acids, for example, such as telocollagen. Copolymer materials containing collagen materials are described in U.S. Patent Nos. 5,65 4,349, 5,910,537, and 5,661,218. Colamers may be desirable in certain embodiments due to their stability against radiation. Hydrogels are associated with calcification (hydroxyapatite deposition). Modified biomolecules such as collagen, when incorporated into the lens, can attract and retain fibronectin to form a protective layer. This (patient-specific) protective layer of fibronectin is not recognized as a foreign body, thus reducing the susceptibility of the lens to calcification. Therefore, by providing a radiologically resistant and biologically active material as a component of the lens, a lens can be obtained that has particularly excellent stability against photo-degradation and biocompatibility. Forming the polymer body may include mixing a non-ionic acrylic monomer with an ionic monomer (such as an acid such as formic acid). The weight ratio of the non-ionic acrylic monomer to the ionic monomer can range from about 10:1 to about 10,000:1, for example, from 50:1 to 200 :1, for example, 75:1, 100:1, 125:1, 150:1, or 175:1. Additional steps in an exemplary method of preparing an exemplary material are described in U.S. Patent Application No. 62 / 765,088, the priority of which is claimed herein, and the disclosure of which is incorporated herein by reference for all purposes. Accordingly, once the polymer is formed, the IOL (or other lens) can be manufactured by conventional methods using, for example, a lathe and a mill, or using a mold, and then subjected to a second irradiation process to provide a radiologically resistant and biologically active material as a component of the lens, a lens can be obtained that has particularly excellent stability against photo-degradation and biocompatibility. to provide a radiologically resistant and biologically active material as a component of the lens, a lens can be obtained that has particularly excellent stability against photo-degradation and biocompatibility.

[0103] to provide a radiologically resistant and biologically active material as a component of the lens, a lens can be obtained that has particularly excellent stability against photo-degradation and biocompatibility. a mill, or using a mold, and then subjected to a second irradiation process to provide a radiologically resistant and biologically active material as a component of the lens, a lens can be obtained that has particularly excellent stability against photo-degradation and biocompatibility. a mill, or using a mold, and then subjected to a second irradiation process a mill, or using a mold, and then subjected to a second irradiation process a mill, or using a mold, and then subjected to a second irradiation process a mill, or using a mold, and then subjected to a second irradiation process

[0104] a mill, or using a mold, and then subjected to a second irradiation process a mill, or using a mold, and then subjected to a second irradiation process It can be modified using

[0105] The RI change as a function of the absorbed radiation is affected by factors such as the concentration of anionic components such as methacrylic acid and acrylic acid that are crosslinked to the copolymer. The concentration of the anionic component affects the swelling coefficient, which in turn affects the RI. More swelling correlates with a lower RI, and a higher concentration of anionic components results in more swelling (and thus a lower RI). The concentration of bication in the physiological and BSS ranges is 0.7 - 2.0 m mol / L of magnesium and 1 - 3.5 mmol / L of calcium. The tendency of the material to swell is determined by anionic components such as methacrylic acid and acrylic acid crosslinked to the copolymer. Excess monomers are usually removed during the extraction process.

[0106] By varying the ratio of two different monomers, the absorbed dose, and the electron energy within a moderate range, different balances of properties within the resulting GRIN lens can be achieved. In this way, a desired RI profile can be created within the lens. As an example, the optical aberrations of a patient's visual system can be measured using a device such as a wavefront aberrometer, and the lens required to correct the aberrations can be calculated. Subsequently, a three - dimensional irradiation plan can be established, from which the dose at any point in the lens can be calculated as a function of the electron energy, and an irradiation plan consisting of the beam position and angle, the electron flux, and the electron energy can be created. Lenses for various patients can be manufactured from a single design of a single refractive index lens, or the geometric characteristics of the lens can be used as an additional degree of freedom (design parameter). Thus, the aspects of this specification A method that can create a variety of lenses based on a desired refractive index profile using a method has great flexibility.

[0107] U.S. Patent Nos. 9,545,340, 9,492,323, 9,144,491 , 9,060,847, 8,932,352, 8,901,190, 8, 617,147, 8,512,320, 8,486,055, 8,337, 553, and 7,789,910 relate to the use of lasers to change the refractive index of lenses, and all of these are hereby incorporated by reference into this specification.

Examples

[0108] An exemplary polymer may be a copolymer having a structure formed from hydroxyethyl methacrylate monomer as a main component and acrylic acid as a minor component. The weight ratio may be as described above. Figure 12 shows a portion of a polymer chain having an acrylic acid side chain (left) and a methacrylate side chain (right). The copolymer is produced during chemical or (the above-mentioned) nuclear irradiation and is then modified using the electron beam irradiation method (or other ionization energy sources) described herein to create a GRI lens.

[0109] According to the generalized formula presented above, other combinations of copolymers can be used to achieve the same final properties. An absorption dose-sensitive radiation refractive index-changing copolymer composition containing a methacrylic ionic monomer and a methacrylic non-ionic monomer sensitive to electron beam impact can be used to prepare materials having various refractive indices that are also suitable for use in the eye.

[0110] The term "low energy" as used herein is a broad term and includes, but is not limited to, 500 eV ~10 keV.

[0111] The term "high energy" as used herein is a broad term and includes, but is not limited to, 10 keV ~700 keV.

[0112] The description and examples in this specification show in detail exemplary embodiments of the present disclosure. Those skilled in the art will recognize that there are numerous variations and modifications of the invention described herein that are within its scope. Therefore, the description of the exemplary embodiments should not be considered as limiting the scope of the invention described herein and should not be so regarded.

[0113] The exemplary embodiments described in the detailed description, drawings, and claims are not meant to be limiting. The teachings herein can be applied in many different ways, for example, to include what is defined and covered by the claims. The aspects herein can be embodied in a variety of forms, and it should be apparent that any particular structure, function, or both disclosed herein are merely representative. Based on the teachings herein, those skilled in the art should understand that the aspects disclosed herein can be implemented independently of other aspects, and two or more of these aspects can be combined in various ways . For example, those skilled in the art can use any reasonable number or combination of the aspects described herein to implement a system or apparatus or to perform a method. Further, in addition to or in place of one or more of the aspects described herein, other structures, functions, or both structures and functions can be used to implement such a system or apparatus or to perform such a method . The aspects herein can be embodied in a wide variety of forms, and it should be apparent that any particular structure, function, or both disclosed herein are merely representative . It should be understood that based on the teachings herein, the aspects disclosed herein can be implemented independently of other aspects, and two or more of these aspects can be combined in various ways . For example, those skilled in the art can use any reasonable number or combination of the aspects described herein to implement a system or apparatus or to perform a method . Further, in addition to or in place of one or more of the aspects described herein, other structures, functions, or both structures and functions can be used to implement such a system or apparatus or to perform such a method . For example, those skilled in the art can use any reasonable number or combination of the aspects described herein to implement a system or apparatus or to perform a method . Additionally, in addition to or in place of one or more of the aspects described herein, other structures, functions, or both structures and functions can be used to implement such a system or apparatus or to perform such a method . ​​ may be. Without departing from the spirit or scope of the subject matter presented in this specification, other embodiments may be utilized and other changes may be made. The aspects of the present disclosure generally described herein and shown in the figures can be arranged, substituted, combined, and designed in a variety of different configurations, and all of them are explicitly contemplated and are readily understood as part of the present disclosure. Since other embodiments may be included in the present disclosure and the claims, it should be understood that the disclosed embodiments are not limited to the examples described below.

[0114] Although the present disclosure has been illustrated and described in detail in the drawings and the foregoing description, such illustrations and descriptions should be considered illustrative and not restrictive. The present disclosure is not limited to the disclosed embodiments. Variations of the disclosed embodiments can be understood and implemented by those skilled in the art who practice within the scope of the disclosed claims from the drawings, the disclosure, and the appended claims.

[0115] All references cited herein are hereby incorporated by reference in their entirety into this specification. Publications and patents or patent applications incorporated by reference are intended to replace and / or supersede such conflicting materials to the extent they conflict with the disclosure contained herein.

[0116] When a range of values is provided, the upper and lower limits, and each value intervening between the upper and lower limits of the range are understood to be included in the embodiments.

[0117] Furthermore, when rules similar to "at least one of A, B, and C" exist, generally ​​​Such a configuration is intended in the sense that a person skilled in the art will understand the rule (e.g., a system having at least one of A, B, and C includes systems having only A, only B, only C, A and B together, A and C together, B and C together, and / or A, B, and C together, etc., but is not limited thereto). When there are similar rules for "at least one of A, B, or C, etc.", generally such a configuration is intended in the sense that a person skilled in the art will understand the rule (e.g., a system having at least one of A, B, or C includes systems having only A, only B, only C, A and B together, A and C together, B and C together, and / or A, B, and C together, etc., but is not limited thereto). ​

Claims

1. A method for inducing non-uniform crosslinking density in a polymer material, comprising: providing a pre-crosslinked three-dimensional polymer matrix comprising a plurality of crosslinks, the three-dimensional polymer matrix being a three-dimensional polymer matrix that does not contain chemical crosslinking agent molecules; irradiating the pre-crosslinked three-dimensional polymer matrix with ionization energy to break at least a portion of the plurality of crosslinks without the need for cleavage of bonds by chemical crosslinking agent molecules, thereby forming a non-uniform crosslinking density within the three-dimensional polymer matrix.

2. The method of claim 1, further comprising, after the irradiating step, placing the three-dimensional polymer matrix in a hydration solution to cause non-uniform swelling of the three-dimensional polymer matrix, thereby generating a non-uniform refractive index within the three-dimensional polymer matrix.

3. The non-uniform refractive index within the three-dimensional polymer matrix produces an anti-reflection surface layer having a thickness of 50 nm to 100 μm, according to the method of claim 2.

4. The non-uniform refractive index within the three-dimensional polymer matrix, when in the eye, focuses light from a wide range of distances with an optional convergence of 0 to 3D, optionally 0 to 2.5D, optionally 0 to 2D, optionally 0 to 1.5D, without causing the three-dimensional polymer matrix to move or change shape while adapting the three-dimensional polymer matrix, according to the method of claim 2.

5. The method of claim 2, further comprising, after placing the three-dimensional polymer matrix in a hydration solution, implanting the three-dimensional polymer matrix into the eye.

6. Implanting the three-dimensional polymer matrix into the eye does not cause a substantial change in the swelling of the three-dimensional polymer matrix, according to the method of claim 5.

7. Placing the three-dimensional polymer matrix in a hydration solution includes implanting the three-dimensional polymer matrix into the eye, wherein the hydration solution comprises aqueous humor of the eye, according to the method of claim 2.

8. Placing the three-dimensional polymer matrix in a hydration solution includes placing the three-dimensional polymer matrix in a balanced salt solution, according to the method of claim 2.

9. The irradiation step includes irradiating the already crosslinked three-dimensional polymer matrix with at least one of an electron beam, X-rays, and beta rays, the method according to claim 1.

10. The irradiation step includes maintaining the three-dimensional polymer matrix in a stationary position and moving an ionization energy source in at least one direction, the method according to claim 1.

11. The irradiation step includes maintaining the ionization energy source in a stationary position and moving the three-dimensional polymer matrix in at least one direction, the method according to claim 1.

12. The irradiation step generates a non-uniform crosslink density substantially throughout the three-dimensional polymer matrix, the method according to claim 1.

13. The irradiation step generates a first region of the three-dimensional polymer matrix having a first crosslink density that is less than a second crosslink density of a second region of the three-dimensional polymer matrix, the method according to claim 1.

14. The first region is a surface layer of the three-dimensional polymer matrix, the method according to claim 13.

15. The irradiation step is performed after the tactile portion is integrally formed with the three-dimensional polymer matrix, the method according to claim 1.

16. The irradiated three-dimensional polymer matrix is dimensionally stable with respect to steam sterilization as part of a wet compress and is hydrolytically stable during long-term use, the method according to claim 1.

17. The three-dimensional polymer matrix includes at least one nonionic acrylic monomer and at least one ionic monomer, the method according to claim 1.

18. The at least one nonionic acrylic monomer is hydroxyethyl methacrylate, The at least one ionic monomer is an acrylic monomer, the method according to claim 17.

19. The three-dimensional polymer matrix includes a collagen material, the method according to claim 1.

20. A method of forming an intraocular lens having an optical system with a non-uniform refractive index, comprising: providing an already crosslinked optical system including a three-dimensional polymer matrix having a plurality of crosslink bonds; An irradiation step of irradiating the already crosslinked optical system with ionization energy to cut at least a part of the plurality of crosslinks, thereby forming a non-uniform crosslink density in the three-dimensional polymer matrix; After the irradiation step, a step of placing the optical system in a hydration solution to cause non-uniform swelling of the three-dimensional polymer matrix, thereby generating a non-uniform refractive index in the optical system; The irradiation step includes irradiating the already crosslinked three-dimensional polymer matrix with at least one of an electron beam, X-rays, and beta rays. **Claim 21**: A method of forming an intraocular lens having an optical system with a non-uniform refractive index, providing an already crosslinked optical system including a three-dimensional polymer matrix having a plurality of crosslinks; an irradiation step of irradiating the already crosslinked optical system with ionization energy to cut at least a part of the plurality of crosslinks, thereby forming a non-uniform crosslink density in the three-dimensional polymer matrix; after the irradiation step, a step of placing the optical system in a hydration solution to cause non-uniform swelling of the three-dimensional polymer matrix, thereby generating a non-uniform refractive index in the optical system; the irradiation step is performed before implanting the optical system into the eye.

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