HK1220773B - Process for manufacture of a photochromic contact lens material - Google Patents

Description

Method for manufacturing photochromic contact lens materials

This application is a divisional application entitled "method for manufacturing thermochromic contact lens materials" having application number 201180018703.1.

Related patent application

This application claims priority to U.S. provisional patent application number 61/323,426 filed on 13/2010 and U.S. patent application serial No. 13/082,517 filed on 8/4/2011.

Technical Field

In one embodiment, the present invention relates to a method for manufacturing a contact lens comprising at least one thermochromic compound. More particularly, the method relates to a method of manufacturing a contact lens comprising a thermochromic compound by photocuring a polymerizable mixture in the presence of the thermochromic compound.

Background

The precision spectral filter may filter specific wavelengths of visible or ultraviolet radiation. This enables the production of optical articles, such as spectacles, which can be tailored to block light of specific wavelengths to produce optical articles for different uses, including the protection of the cornea, lens and retina from specific harmful wavelengths of radiation. For example, a variety of sunglasses have been used to protect human eyes from glare, including photochromic glasses, polarized glasses, and glasses used for certain activities, including shooting and fishing. Photochromic lenses darken when exposed to certain wavelengths of light and typically Ultraviolet (UV) light and brighten when the UV light is removed. Typically, such photochromic eyewear includes prescription eyewear for vision correction.

It is more difficult to apply certain techniques, including photochromic techniques, to contact lenses than to apply the same techniques to spectacles. Additional factors such as oxygen permeability, comfort and fit of the resulting contact lens must be considered. The manufacturing process for contact lenses is also more complicated. Contact lenses are typically formed by irradiating a photoinitiator in the presence of one or more polymerizable materials. For photochromic contact lenses, it is desirable to include the photochromic dye in a reactive mixture comprising a photoinitiator and a polymerizable material, which upon polymerization can form the contact lens. Unfortunately, certain dyes (including photochromic dyes) have the potential to interfere with photoinitiator activation.

The polymerizable mixture may also be cured using other free radical based chain polymerization reactions, including thermal polymerization.

Disclosure of Invention

In one form of the invention, the invention includes a method for manufacturing a contact lens comprising at least one thermochromic compound. The method includes (1) selecting a photoinitiator that absorbs radiation at a first wavelength and a thermochromic compound that absorbs radiation at the same first wavelength but does not substantially absorb radiation at the wavelength at a second temperature, (2) maintaining the reaction mixture at the second temperature, and (3) exposing the reaction mixture to radiation including the first wavelength.

Drawings

The invention is disclosed with reference to the accompanying drawings, in which:

FIG. 1 is a flow chart depicting a method of the present invention;

FIGS. 2A and 2B are perspective and outline views of a tray for use with the present invention;

FIG. 3 is an absorption spectrum of a photochromic dye, photoinitiator, and filter of an embodiment;

fig. 4A and 4B are absorption spectra of dyes in an activated state or an unactivated state.

FIG. 5 depicts the profile of various contact lenses cured at various temperatures;

FIG. 6 is a schematic view of an apparatus for curing contact lenses;

FIGS. 7A to 7D depict contact lenses cured under various conditions as described in examples 5-8;

FIGS. 8A and 8B are graphs of the amount of residual monomer remaining in a contact lens;

FIGS. 9A and 9B are graphs of absorption spectra and rheological properties of a contact lens forming process;

FIGS. 10A and 10B are graphs of absorption spectra and rheological properties of another contact lens forming method; and

fig. 11A and 11B are graphs of absorption spectra and rheological properties of another contact lens forming method.

Corresponding reference characters indicate corresponding parts throughout the several views. The examples set forth herein illustrate several embodiments of the invention, but should not be construed as limiting the scope of the invention in any way.

Detailed Description

Any chemical name with a (meth) prefix (e.g., (meth) acrylate) includes both unsubstituted compounds and methyl-substituted compounds.

The compound that absorbs the fixing light is a compound that exhibits temperature-independent light absorption.

Referring to fig. 1, one embodiment 100 of the method is depicted, beginning with step 102, in which a photoinitiator and a photochromic dye are selected. Although it is theoretically possible to select initiator/photochromic dye pairs that do not have any overlap in their absorption spectra, such initiator/photochromic dye pairs are difficult to use in contact lenses. In one embodiment, the present invention relates to initiator/thermochromic compound pairs that absorb in overlapping wavelength ranges at least one temperature. In one embodiment, the initiator/dye pairs exhibit overlapping absorption at least one wavelength ranging from about 380nm to about 780 nm.

Suitable visible light Photoinitiators are known in the art and include, but are not limited to, aromatic α -hydroxy ketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphine oxides, and tertiary amine plus diketones, mixtures thereof, and the like, illustrative examples of Photoinitiators are 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis (2, 6-dimethoxybenzoyl) -2, 4-4-trimethylpentylphosphine oxide (DMBAPO), bis (2,4, 6-trimethylbenzoyl) -phenylphosphine oxide (Irgacure), 2,4, 6-trimethylbenzyldiphenylphosphine oxide and 2,4, 6-trimethylbenzoyldiphenylphosphine oxide, and benzoin methyl ester and benzyl ether, and mixtures of such initiators available from the company of the trade name of Irgacure, as the weight initiators, as described in the visible light polymerization initiator systems available from the company of the trade name of Sorbouchure & lt [ sic ] Irgacure [1, Irgacure ] and mixtures of such initiators available in the fields as the weight of the photopolymerization initiators from the company of the company name of the company Souchi, the family of the company of the family of the patents entitled photoinitiator, the photopolymerization initiators, the photoinitiator, the initiator, the family of the patents entitled photoinitiator, the photoinitiator, and the photoinitiator, and the photoinitiator, and photoinitiator, including the photoinitiator, and photoinitiator, the photoinitiator, and photoinitiator, the.

In one embodiment, the visible light photoinitiator comprises α -hydroxyketone such as Irgacure available from CIBA^®(e.g., Irgacure 1700 or 1800); various organic phosphine oxides, 2' -azo-diisobutyronitrile; diethoxyacetophenone; 1-hydroxycyclohexyl phenyl ketone; 2, 2-dimethoxy-2-phenylacetophenone; phenothiazine; diisopropyl xanthogen disulfide; benzoin or a benzoin derivative; and so on. In a fruitIn embodiments, the initiator may absorb light and activate at wavelengths below about 420 nm.

In another embodiment, a thermal initiator is used in place of or in combination with a photoinitiator. Examples of thermal initiators include lauroyl peroxide, benzoyl peroxide, isopropyl peroxycarbonate, azobisisobutyronitrile, mixtures thereof, and the like.

Thermochromic compounds are compounds that exhibit temperature-dependent light absorption. Thermochromic compounds include compounds such as leuco dyes and liquid crystal particles, which are generally used because of temperature-dependent changes in their light absorption, and compounds such as photochromic compounds, which show changes in their absorbance or absorbance in their activated state.

Examples of thermochromic liquid crystals include cholesteryl nonanoate and cyanobiphenyl. Further examples are disclosed in "liquid crystals", d. Demus and h. Sackman, Gordon and break 1967. Examples of leuco dyes include spirolactones, fluorans, spiropyrans, fulgides, and combinations thereof. The liquid crystal and leuco dye may be incorporated into the polymerizable mixture in microcapsules.

Photochromic dyes are any compound that can switch between a first "clear", "bleached" or "unactivated" ground state to a second "colored", darkened or "activated" state in response to the absorption of certain wavelengths of electromagnetic radiation (or "actinic radiation"). In one embodiment, the photochromic dye, when in an activated state, can absorb in the visible range of the electromagnetic spectrum (380 nm to 780 nm). Examples of suitable photochromic dyes are known in the art and include, but are not limited to, the following classes of materials: chromenes, such as naphthopyrans, benzopyrans, indenonaphthopyrans, and phenanthropyrans; spiropyrans, such as spiro (benzindolinyl) naphthopyrans, spiro (indolinyl) benzopyrans, spiro (indolinyl) naphthopyrans, spiro (indolinyl) quinopyrans and spiro (indolinyl) pyrans;oxazines, e.g. spiro (indoline) naphthoOxazines, spiro (indoline) pyrido-benzoxazinesOxazines, spiro (benzindolinyl) pyrido-benzoxazinesOxazine, spiro (benzindoline) naphthoOxazine and spiro (indoline) benzoxazinesAn oxazine; mercury dithizonates, fulgides, fulgimides and mixtures of such photochromic compounds.

Additional suitable photochromic dyes include, but are not limited to, organometallic dithizone complexes, such as (arylazo) -thioformylarylhydrazine complexes, such as mercury dithizone; and fulgide, fulgimide and naphthoOxazines, spirobenzopyrans; polymerizable spirobenzopyrans and spirobenzopyrans; a polymerizable fulgide; a polymerizable naphthonaphthalenedione; polymerizable spiroAn oxazine; and polymerizable polyalkoxylated naphthopyrans. The photochromic dye may be used alone or in combination with one or more other suitable and complementary photochromic dyes.

Other useful photochromic dyes include indeno-fused naphthopyrans selected from the group consisting of indeno [2',3':3,4] naphtho [1,2-b ] pyrans and indeno [1',2':4,3] naphtho [2,1-b ] pyrans, which are more specifically disclosed in US2009/0072206 and US2006/0226401, and those cited in US7,364,291, and combinations thereof. Other suitable photochromic compounds are disclosed in US7,556,750, the disclosure of which is incorporated herein by reference. Non-limiting examples of suitable photochromic dyes include naphthopyrans, such as those shown in table 1. The dyes may include polymerizable functional groups such that they polymerize into the resulting contact lens. Examples of the polymerizable functional group include (meth) acrylate, (meth) acrylamide, vinyl-containing substance, and the like. In one embodiment, a photochromic dye is selected that absorbs across the entire visible spectrum when in the activated state, but absorbs below about 430nm and less than about 10% of the entire visible spectrum when not activated.

The amount of thermochromic compound used will be an amount effective to achieve the desired percent reduction in transmission at the particular wavelength at which the selected thermochromic compound is activated. The specific amount used will also depend on the tint strength and molar absorption coefficient of the selected compound, the lens material selected, and the thickness of the lens.

In another embodiment, the contact lens may contain a mixture of thermochromic compounds, at least one thermochromic compound mixed with other light-absorbing compounds (including pigments, dyes, and UV-absorbing compounds), or may contain multiple layers of thermochromic compounds, such as for making polarized lenses.

Once the photoinitiator and thermochromic compound have been selected, step 104 is performed in which a mixture of contact lens forming materials is disposed in a mold. Step 104 is described in more detail with reference to fig. 2A and 2.

Referring to fig. 2A, the reaction mixture 200 is disposed in a mold 202, which is comprised of a tray 204And (4) supporting. In one embodiment, the mold is a thermoplastic optical mold made of any suitable material (including, but not limited to, polypropylene, polystyrene, and/or Zeonor)^®: a cycloolefin polymer resin). In certain embodiments, the mold is selected to be transparent to the wavelength of the activatable photoinitiator, allowing for illumination from the bottom side of the mold. In other embodiments, such as those utilizing thermal initiation, the mold 202 is optically opaque. A "reaction mixture" is a mixture of components that can form a polymer when subjected to polymer forming conditions, including reactive components, diluents (if used), initiators, crosslinkers, and additives. Reactive components are components in the reaction mixture that, upon polymerization, become permanent parts of the polymer through chemical bonding or entrapment or entanglement within the polymer matrix. For example, reactive monomers become part of the polymer through polymerization, while non-reactive polymer internal wetting agents (such as PVP) become part of the polymer through entrapment. The diluent (if used) and any additional processing aids do not become part of the polymer structure nor are they part of the reactive components. Mixture 200 includes one or more polymerizable monomers suitable for forming a contact lens. Such monomers are known in the art and are generally selected for preparing polymeric products having high water and oxygen permeability.

The present invention can be used to provide hard or soft contact lenses made of any known lens material or materials suitable for making such lenses. Preferably, the lenses of the invention are soft contact lenses having a water content of from about 0% to about 90%, and in another embodiment, from about 20% to about 75% water. In yet another embodiment, the contact lenses of the invention have a water content of at least about 25%. The lenses of the invention may also have other desirable properties, including a tensile modulus of less than about 200psi, in some embodiments, less than about 150psi, and in other embodiments, less than about 100 psi. These lenses may also have an oxygen permeability of greater than about 50psi, and in some embodiments, greater than about 100 psi. It will be appreciated that combinations of the aforementioned properties are desirable and that the ranges mentioned above may be combined in any combination.

In one embodiment, the lens is made from a hydrophilic component, a silicone-containing component, and mixtures thereof to form a polymer such as a silicone, hydrogel, silicone hydrogel, and combinations thereof. Materials useful for forming the lenses of the invention can be prepared by reacting a blend of macromers, monomers, polymers, and combinations thereof, along with additives (e.g., polymerization initiators). Suitable materials include, but are not limited to, silicone hydrogels made from silicone macromers and hydrophilic monomers.

Reaction mixtures for the preparation of contact lenses are known, and the components of such mixtures are commercially available. Exemplary polymers suitable for forming contact lenses include, but are not limited to, etafilcon A, genfilcon A, lenefilcon A, polymacon, balafilcon, acquafilcon, comfilcon, galyfilcon, senofilcon, narafilcon, and lotrafilcon. In another embodiment, a contact lens formulation comprises etafilcon, senofilcon, balafilcon, galyfilcon, lotrafilcon, comfilcon, filcon II 3, asmofilcon a, and a silicone hydrogel, prepared as described in the following patents: U.S. patent number 5,998,498; U.S. patent application number 09/532,943, a continuation-in-part of U.S. patent application number 09/532,943 filed on 30/8/2000, and U.S. patents nos. 6,087,415, U.S. 6,087,415, U.S. 5,760,100, U.S. 5,776, 999, U.S. 5,789,461, U.S. 5,849,811, U.S. 5,965,631, U.S. 7,553,880, WO2008/061992, and US 2010/048847. These patents are hereby incorporated by reference herein with respect to the hydrogel compositions contained therein.

In one embodiment, the reaction mixture used is a HEMA-based hydrogel, such as etafilcon a. Etafilcon a (disclosed in U.S. patent numbers 4,680,336 and 4,495,313, which are incorporated herein by reference in their entirety) is generally a formulation of: 100 parts by weight ("pbw") HEMA, about 1.5 to about 2.5pbw MAA, about 0.3 to about 1.3pbw ethylene glycol dimethacrylate, about 0.05 to about 1.5pbw 1,1,1, -trimethylolpropane trimethacrylate, and about 0.017 to about 0.024pbw visible color. The phrase "polymerizable monomer" includes monomers having a large molecular weight, sometimes referred to as macromers. Reaction mixtures of different polymerizable monomers can also be used, resulting in the formation of copolymers.

In one embodiment, the mixture 200 further comprises one or more selected visible light photoinitiators that are activated by exposure to visible light to initiate a chain reaction that causes the above-described monomers to polymerize.

The mixture 200 also includes selected thermochromic compounds, including in one embodiment photochromic dyes that become colored upon exposure to light but will return to their original color soon after the light is terminated. In its non-activated (light transmitting) state, the dye absorbs below about 430nm and becomes activated. Upon activation, the absorption range becomes overlapping with the light-accessible spectrum (380-780nm) and thus becomes colored. This color in turn just blocks wavelengths that would otherwise activate photoinitiators that typically absorb below about 420 nm.

The presence of both the thermochromic compound and the photoinitiator in the same reaction mixture can make controllable activation of the photoinitiator problematic. Without wishing to be bound by any particular theory, applicants believe that activating the thermochromic compound in the same spectral region as the photoinitiator results in the dye at least partially "shading" the photoinitiator. Incomplete activation of the initiator can hinder curing and/or result in uneven or anisotropic curing that can lead to the formation of material defects and stresses within the lens. These defects can adversely affect the mechanical and optical properties of the resulting contact lens. In one embodiment of the present invention wherein the thermochromic compound comprises at least one photochromic compound, the method utilizes a filter to remove at least a portion of the wavelengths that cause excitation of the dye while transmitting wavelengths that can activate the photoinitiator. See step 106 of fig. 1. Step 106 is illustrated in more detail in fig. 3.

Suitable filters are selected based on the spectra of the photochromic dye and photoinitiator. Referring to fig. 3, the spectrum of the dye 300 is compared to the spectrum of the photoinitiator 302 and the spectrum of light from a particular light source 304. A filter is used that allows transmission of the selected wavelength of light (line 306). In the example of FIG. 3, the photoinitiator is Irgacure^®1700 light source is TL03 lamp and photochromic dye is dye-1. In this case, the photoinitiator 302 may be preferentially activated in the presence of the dye 300 by providing curing light to the mixture at a wavelength above 400 nm.

Although the dye 300 is somewhat active between 400nm and 420nm, the photoinitiator 302 is more responsive (i.e., has greater molar absorbance) than the dye at this wavelength. At least a portion of the wavelength that activates the dye (e.g., wavelengths below 400 nm) is omitted. In one embodiment, a long pass filter is used to slightly remove wavelengths below about 400nm but transmit wavelengths above about 400 nm. In another embodiment, a different bandpass filter is used to transmit only wavelengths in the range of about 400nm to about 420nm, but remove wavelengths outside this range. In another embodiment, the bandpass filter selects wavelengths in the range of about 420 to about 440 nm. These wavelengths are selected according to the spectra given in figure 3 for the particular photochromic dye and photoinitiator shown therein. In other embodiments, different frequencies are selected to allow preferential excitation of photoinitiators having different absorption spectra. Examples of suitable filters include a SCHOTT GG420 filter or an Encapsulite C20 filter. In other embodiments, the light source is selected so as to provide curing light that is not illuminated within the absorption wavelength of the unactivated dye and filtering is not necessary. Examples of such light sources include custom Light Emitting Diodes (LEDs).

Applicants have found that the optical and mechanical properties of the resulting lens can be further improved by performing the curing process with the thermochromic dye at an activated or less activated temperature (step 108 of fig. 1). For example, and without wishing to be bound by any particular theory, in embodiments where the thermochromic compound is a photochromic compound, it is believed that the elevated temperature maintains the photochromic dye in the off (unactivated) state. Thus, the absorption spectrum of the photochromic dye is different at room temperature when compared to the absorption spectrum of the photochromic dye at high temperature. For photochromic dyes, this will generally result in a lambda at the very same time as the photoinitiator_maxThe molar absorbance decreases at overlapping wavelengths. By maintaining high temperatures during photocuring, an increased amount of dye remains in the off state, thus effectively reducing dye activation that can interfere with the polymerization process. Referring to FIG. 4A, which depicts naphthopyran dye-1 in an inactive state, in FIG. 4B, the dye is in an active state. In fig. 4A, it is evident that the switched-off dye is relatively inactive at wavelengths above 420 nm. In contrast, fig. 4B shows that the activated dye absorbs at wavelengths above 420 nm. A series of photochromic contact lenses were cured at various temperatures using filtered light. See examples 1 to 4 described below. Figure 5 depicts the contours of these lenses.

In another embodiment, wherein the thermochromic dye is a leuco dye such as spirolactones (e.g., crystal violet lactone), fluorans, spiropyrans, and fulgides in combination with a weak acid such as bisphenol a, parabens, 1,2, 3-triazole derivatives, and 4-hydroxycoumarins, curing may be carried out at a temperature between about 5 and 60 ℃. In another embodiment, where the thermochromic dye is a liquid crystal, such as cholesteryl nonanoate or cyanobiphenyl, curing may be carried out at a temperature between about 10 to about 80 ℃.

Referring to the series of lens cross-sections depicted in fig. 5, the lens cured at 45 ℃ (first image, left) showed poor curing with inverted cross-sections that were unacceptable for use on the human eye. The lens cured at 50 ℃ showed some improvement (second image from left). The lens cured at 55 ℃ showed a further improvement (third cross section). The cured lenses at 65 ℃ exhibited only a small flattening in cross section and were found to provide acceptable optical properties. These results demonstrate the improvement in corneal contact lens profile and optical properties when the lens is cured at elevated temperatures. Thus, given the teachings of the present patent application, the desired temperature range can be selected to produce acceptable profiles and optical properties for each particular reaction mixture.

For example, when a photochromic dye (e.g., dye-1, a naphthopyran photochromic compound shown in Table 1) is used, a curing temperature range of about 55 ℃ to about 90 ℃ may be used. In another embodiment, a temperature range of about 65 ℃ to about 80 ℃ is used. In yet another embodiment, a temperature of about 80 ℃ is used. Other dyes may have different preferred temperature ranges.

Applicants have also found that while filtering light and increasing temperature can improve the properties of the resulting lens, they are not the only factors, at least in some cases. Contact lens properties can also be improved by balancing the light received by the mixture 200 on the exposed side 206 and the mold contact side 208. See fig. 2B. The precise conditions necessary to balance the intensity will depend on the composition and thickness of the reaction mixture, the composition of the tray, and the nature of the filters and light sources. Those of ordinary skill in the art, with the benefit of this disclosure, can determine the optimal balance for a particular formulation.

In some embodiments, for example for contact lenses having low concentrations of thermochromic compounds, a particular balance of light intensity may not be necessary. The mixture is sufficiently thin that the light intensity at the exposed surface and the mold contacting side are substantially the same. In these cases, the resulting cured contact lens is sufficient. Similarly, in some embodiments, it is possible to omit any special balance by limiting the thermochromic compound to a particular area of the lens (e.g., pupil-only thermochromic lenses).

In some cases, the light intensity at the mold-contacting side is substantially lower than at the exposed surface-presumably due to absorption of light by the thermochromic compound as the light passes through the mixture. In these cases, the profile of the resulting lens is less than satisfactory. A second light source may be added to illuminate the optically transparent mold from below to properly balance the light intensity. Figure 6 depicts such a system.

Referring to fig. 6, two filters 600, 602 are used to both filter the wavelength of light emitted from one or more light sources 604, 606 and balance the intensity of the light before such light illuminates the reaction mixture 200. The tray 204 allows the wavelengths used to activate the photoinitiator to pass through the bottom of the tray, thereby allowing the reaction mixture within the mold 202 to be irradiated from both the exposed side 206 and the mold-contacting side 208 (see fig. 2B). The light source, filter and tray are arranged so that equal light intensities are delivered to both the exposed side and the mold contacting side of the mixture. In one embodiment (not shown), the tray 204 acts as a filter and removes certain wavelengths, thus eliminating the need for the filter 602.

In some embodiments, the intensity of one of the light sources is increased to correct for the loss of light intensity between the light source and the mixture 200. For example, in such embodiments, the bottom light source 606 may have a higher intensity than the top light source 604 to correct for light intensity losses due to bottom light passing through or shadowing by the tray 204. For example, and not by way of limitation, the intensity of the top light source 604 may be about 1mW/cm²And the intensity of the bottom light source may be about 2mW/cm². Different intensity values are selected depending on the amount of light blocked by each filter and the transmission coefficient or shading of the tray 204. Similarly, a filter that reduces the intensity of light can be used to balance the intensity of light that actually reaches the reaction mixture.

Fig. 7A to 7D show the effect of balanced or unbalanced illumination. Figure 7A shows the desired profile of a properly shaped contact lens that does not include a photochromic dye. Figure 7B shows the profile of a contact lens prepared without a filter and cured from the top side only. Figure 7C shows the profile of a contact lens prepared using a filter and curing from the top side only. Although not apparent in fig. 7C, the lens is inverted. Figure 7D shows the profile of a contact lens prepared by curing from both sides using a filter, but with unbalanced light intensity. See examples 5 to 9.

After curing is complete, the lens is removed from the mold and may be treated with a solvent to remove the diluent (if used) or any trace amounts of unreacted components. In one embodiment, solvent removal is performed with a predominantly aqueous solution. The lens is then hydrated to form a hydrogel lens.

Using the techniques described above, several forms of contact lenses can be prepared. In some embodiments, the thermochromic compound is uniformly dispersed throughout the resulting contact lens. In such an embodiment, the entire contact lens is thermochromic. In other embodiments, only the central portion of the resulting contact lens comprises a thermochromic compound. Since the central portion is above the pupil, the resulting contact lens is a pupil-only thermochromic contact lens. The central portion or central circular zone can be the same size as the optic zone, with the optic zone diameter of a typical contact lens being about 9mm or less. In one embodiment, the central circular region has a diameter of between about 4 to about 9mm, in another embodiment between about 6 to about 9mm, and in another embodiment between about 6 to about 8 mm.

The dye can be disposed by a variety of techniques to provide a region having a defined diameter. For example, the dye-containing composition can be applied to at least a portion of the mold surface by pad printing, ink jetting, spin coating, or the like. In these embodiments, the dye composition may comprise additional known useful components, including binding polymers (which may be reactive or non-reactive), solvents, and optionally polymerizable components, chain transfer agents, initiators, and combinations thereof. The dye composition may be reacted with the reactive mixture or the dye composition may swell and become entangled by the reactive mixture. If the dye composition is reactive, the dye composition may be partially or fully cured prior to dispensing the reactive mixture into the mold. If the dye composition is non-reactive, it may be desirable to distill off some or all of the solvent prior to dispensing the reactive mixture. The type and concentration of non-dye components of the dye composition known in the art may be used in the present invention. Examples include those disclosed in EP1448725, WO01/40846, US5658376, US20090244479, WO2006/110306 and 6,337,040.

If an initiator is included in the dye composition, the initiator and thermochromic compound are selected to have absorption profiles that do not substantially overlap at the selected curing temperature. Multiple layers of the dye composition can be applied to the mold, each layer can be free of thermochromic compounds, contain the same thermochromic compound, or different thermochromic compounds. An example of this embodiment is a dye composition applied in alternating layers, each layer containing liquid crystals, to form a polarized contact lens. In this embodiment, the alternating layers are cured under different conditions to provide layers in which the liquid crystals have alternating orientations, thereby producing the desired polarizing effect. In another embodiment, multiple layers of the same thermochromic compound are applied, each layer centered but having a different diameter, to produce a lens with a progressive concentration of thermochromic compound.

After pre-curing the cured composition or evaporating off the solvent, the reaction mixture is metered into the mold as described above. The reactive mixture may comprise at least one additional thermochromic compound, which may be the same or different from the thermochromic compound used in the dye composition layer. Alternatively, the reactive mixture may be free of thermochromic compounds. After the dosing of the reactive mixture, the reactive mixture is cured.

Examples of suitable diameters include 4mm, 6mm, 9mm and 11.4 mm. In one embodiment, the reactive mixture containing the photochromic dye is deposited or dispensed by microdosing application, such as disclosed in the following patents: US7560056 and U.S. patent application No. 13/082,447 entitled "Pupil-Only Photochromic Contact Lenses displaying separable Optics and Comfort," both of which were filed concurrently on 8/4.2011.

To support the theory of operation, several experiments were performed in which the time required to cure the mixture was measured as a function of increasing dye concentration. The results of these experiments demonstrate that higher dye concentrations result in extended cure times. At a dye concentration of about 3% (MXP 7-1631 dye), the mixture did not cure at a temperature of 40 ℃. See example 9. This supports the hypothesis that dyes can interfere with the activation of photoinitiators.

To further support the theory of operation, a series of lenses prepared by pad printing and no pad printing photochromic dyes were tested for residual monomer concentration. The lenses are cured without hydration as the reaction mixture passes through a curing tunnel where they are irradiated with light as they pass through the zones. After passing a certain number of zones the sample was removed from the apparatus and tested for residual photoinitiator and residual monomer. Thus, samples removed after passing through five curing zones experience a longer residence time than samples removed after passing through two curing zones. See example 11.

The results (shown in fig. 8A) show that the photochromic dye is preventing the initiator from starting the free radical polymerization reaction. Those samples in which the photochromic dye was present exhibited a significantly greater concentration of unpolymerized monomer relative to the corresponding control lacking the photochromic dye. Also, fig. 8B shows that the concentration of the photoinitiator is greater when the photochromic dye is present. It is noteworthy that when photochromic dyes are used, the concentration of the photoinitiator achieves a steady-state concentration that never reaches zero or in other words never coincides with the control.

Similarly, rheological data were obtained for photochromic lenses prepared with or without optical filters. See example 11. The results (fig. 9A and 9B) show the difference in gelation point between lenses prepared using the photochromic dye and lenses prepared without the photochromic dye.

FIG. 9A shows the absorption spectrum of an unactivated photochromic dye (line 900), the absorption spectrum of a photoinitiator (line 904), and a filtered light source with wavelengths below 380nm removed (line 902, λ around 400 nm)_max). Figure 9B plots the rheological data for the photochromic lens (line 906) and the non-photochromic control (line 908), which were cured using the conditions of figure 9A. Interference from the photochromic dye causes the modulus (G) to develop more slowly than the corresponding monomer cured in the absence of the dye, see lines 906 and 908, respectively. Control (908) exhibited a 95% conversion gelation point (point 908 a) of 37 seconds and a 99% conversion gelation point at point 908 b. This gap in percent conversion at the gelation point indicates a significant difference between the photochromic lens and the target control lens. The resulting photochromic polymers are considered unsatisfactory for the preparation of contact lenses.

Fig. 10A is similar to fig. 9A, but differs therefrom in that a different filter is used. In fig. 10A, filtered light 1000 has wavelengths below 400nm removed. Figure 10B plots the rheological data for the photochromic lens (line 1002) and the non-photochromic control (line 908), which were cured using the conditions of figure 10A. The two lines 1002, 908 are substantially closer together than in fig. 9B, thus resulting in a photochromic lens that more closely matches the control lens. The resulting photochromic lenses were considered satisfactory. The 95% conversion gelation point (1002a) and 99% conversion gelation point (1002b) are shown.

FIG. 11A shows non-activationThe absorption spectrum of the photochromic dye (line 900), the absorption spectrum of the photoinitiator (line 904) and the light source (line 1100, λ around 440 nm)_max). The light source 1100 removes wavelengths below 420 nm. Figure 11B plots the rheological data from the photochromic lenses (line 904) and the non-photochromic controls (line 900), the lenses being cured with the conditions of figure 11A. Thus, the light source and filter remove wavelengths below about 420nm where the dye responsiveness is highest. As the filter removes lower wavelengths, activation of the dye is minimized and the modulus of the photochromic lens 904 becomes more like that of the control 900.

Examples of the invention

Table 1: general abbreviations

Abbreviations	Compound (I)
		Dye-1
Dye-2
		Dye-3
Dye-4
		TMPTMA	Trimethylolpropane trimethacrylate
EDGMA	Ethylene glycol dimethacrylate
		MAA	Methacrylic acid
HEMA	2-Hydroxyethyl methacrylate
		Norbloc	2- (2' -hydroxy-5-methacryloyloxyethylphenyl) -2H-benzotriazole
Glucam 20	Ethoxylated methyl glucose ethers

Five formulations were used in the examples below. The percentage composition of each sample is shown in table 2:

TABLE 2

The components listed in table 2 were mixed with Glucam 20 in the following amounts: 55% by weight of monomer was mixed with 45% by weight of diluent.

Examples 1 to 45 ℃ curing temperature

The front curve mold (Zeonor) was pad printed with a dye base formed from 7% dye-1 and 93% clear base (49.4% isopropyl lactate, 12.4% 1-ethoxy-2-propanol, 0.9% 1-octanethiol, 1.63% glycerol, 35% HEMA, 0.48% methacrylic acid and 0.21% azobis- (2-methylbutyronitrile) (AMBM)). The clear base was prepared by adding 1-octanethiol, the monomers and the solvents (except for about 50-100cc of isopropyl lactate) and mixing and stirring for 10 minutes in a 5 liter blue-capped bottle. The mixture was then poured into a 5L stainless steel reactor with a stirrer and nitrogen. The mixture was stirred and heated for about 25 minutes until the temperature was 68 ℃. After the temperature had stabilized at 68 ℃, AMBN was dissolved in the remaining isopropyl lactate and added while opening the nitrogen bleed (nitrogen blanket). The polymerization is allowed to proceed for 16-24 hours, and then the temperature is raised to 80 ℃ and the reaction is complete. The mixture was then allowed to equilibrate to room temperature.

The diameter of the stamp was 11.44 mm. The front bending die and the back bending die were degassed with nitrogen. The front curve mold was dosed with the reactive monomer mixture containing control a (see table 2) without dye in RMM. The back curve mold was placed on the front curve with the monomer and the assembled mold was moved to the curing chamber and then heated to a curing temperature of 45 c. The system was allowed to equilibrate for five minutes. Once balanced, the system was set at 3.5mW/cm using a CG420 filter and a Philips TL03 lamp²And curing for ten minutes. The back bend die was removed and the front bend was hydrated in 70 ℃ deionized water for ten minutes. The resulting lenses are subjected to conventional packaging and sterilization processes. The lens was cross-sectioned to obtain an image. The image is shown in fig. 5.

Examples 2 curing temperatures of 50 ℃

Example 2 was carried out in substantially the same manner as example 1, except that the curing temperature was 50 ℃. The lens was cross-sectioned to obtain an image. The image is shown in fig. 5.

Examples 3 curing temperatures of 55 ℃

Example 3 was carried out in substantially the same manner as example 1, except that the curing temperature was 55 ℃. The lens was cross-sectioned to obtain an image. The image is shown in fig. 5.

Examples 4 curing temperatures of 65 ℃

Example 2 was carried out in substantially the same manner as example 1, except that the curing temperature was 65 ℃. The lens was cross-sectioned to obtain an image. The image is shown in fig. 5.

Examples 5 to 8

The front bend die and the back bend die (Zeonor) were degassed with nitrogen. For examples 6-8, the forward curve mold was dosed with a reactive monomer mixture containing 2.1% dye-1 (Table 2, formulation B). For example 5 (control), formulation a was dosed into the lead curve. The back bend die was placed on the front bend with the monomer mixture. The assembled mold was moved to a curing chamber and heated to 65 ℃. The assembly was allowed to equilibrate for five minutes. Once equilibrated, the system was cured with a Philips TL03 lamp and a CG420 filter for ten minutes at the cure intensity and cure setting specified in table 3. The back bend die was removed and the front bend was hydrated in 70 ℃ deionized water for ten minutes. The resulting lenses are subjected to conventional packaging and sterilization processes.

TABLE 3

Example number	Light filter	Apical Strength (mW/cm)2)	Base intensity (mW/cm)2)	Reference numerals	Cross section appearance
						5	Is that	3	0	7A	Is normal
6	Is that		0	7B	Crimping
						7	Is that	2.8	0.8	7C	Reverse, abduct
8	Is that	2.8	2.8	7D

Cross-sections of lenses made in examples 5-8 are shown in fig. 7A-D. Figure 7A is a cross section of a lens of example 5 formed without photochromic dye showing a cross section of equilibrium curvature indicating a well-formed round contact lens. Figure 7B is a cross section of a lens formed with photochromic dye, cured only from the top. The lens cross section is crimped into a tube. This indicates that uneven curing occurred, confirming that the effect of the photochromic dye on curing cannot be controlled in this example using the filter alone. Fig. 7C (example 7) and D (example 8) show cross sections of lenses made with both sides cured. In 7C, the lens was inverted, but showed an equilibrium arc, a great improvement over FIG. B. Fig. 7D shows a cross section of a lens cured with balanced intensity and filter on both sides, resulting in a lens with a balanced, curved cross section.

EXAMPLE 9 high dye concentration interferes with curing

The photopolymerization of formulations A-E was monitored using an ATS StressTech rheometer (available from ATS Rheosystems Inc., address: 52 Georgeotown Road, Bordentown, N J08505) equipped with a photocuring attachment comprising a temperature control cell having a lower quartz plate and an upper aluminum plate, and an OmniCure mercury arc lamp (available from EXFO Photonic solutions Inc., address: 2260 Argentia Rd., Mississauga, ON L5N 6H7 CANADA) having a 420nm bandpass filter (available from Andovercorporation, address: 4 Commercl Drive, EM, NH 03079 Sal 2800 USA) located below the quartz plate. Adjusting the intensity of the radiation to 4.5 +/-0.5 mW/cm²The radiation intensity was measured on the surface of the quartz window using an IL1400A radiometer and an XRL140A sensor (available from International Light, Inc., address 17 Graf Road, Newburyport, MA 01950). Each formulation was evaluated at 40 deg.C, 55 deg.C and 70 deg.C.

After approximately 0.25mL of the reactive monomer mixture was placed on the lower plate of the rheometer, the 25mm diameter upper plate was lowered to 0.500 ± 0.001mm above the lower plate and held until the reaction reached the gelation point. The reaction starts by turning on OmniCure after the sample is allowed to reach thermal equilibrium (-5 minutes, determined by the plateau in steady shear viscosity during sample warming). During this time, the sample chamber was purged with nitrogen at 400sccm while the sample was in thermal equilibrium. After this initial purge, with CheckPoint O₂The sensor (PBI Dansensor, available from Topac, Inc.; address: 101 Derby St., #203 Hingham, MA 02043) monitored the oxygen level in the sample chamber at 0.5. + -. 0.1%. During the reaction, the rheometer continuously monitored the strain induced by the applied dynamic stress (fast oscillatory mode), where the strain at the applied sinusoidal stress (applied at a frequency of 1.0 Hz) was measured using a time period of less than a full cycle. The dynamic shear modulus (G'), loss modulus (G ") and gap height were monitored as a function of exposure time. As the reaction proceeds, the shear modulus is increased from<1Pa increase to>0.1Mpa, tan δ (= G "/G') decreases from almost infinity to less than 1. For many reactive crosslinking systems, the gelation point is defined as the point in time when tan δ = 1 (the cross-over point when G' = G "). At the point in time when G' reached 100Pa (shortly after the gelation point), the restriction of the upper plate by the gap height (self-tension mode: tension = 0) was removed so that the gap between the upper and lower plates would change as the reactive monomer mixture shrinks during curing and the stress due to shrinkage was kept at a minimum. The measurement of the change in gap provides an estimate of the amount of shrinkage caused by the polymerization reaction. After 10 minutes of exposure, OmniCure was turned off (i.e., the cure was terminated).

The rheological results for each formulation evaluated are shown in table 4 below.

Table 4: rheological results

Samples C and E failed to cure at 40 ℃. These samples contained 2.8% photochromic dye.

EXAMPLE 10 monitoring of polymerization progress through the Tunnel region

One protocol was performed to determine the consumption rate of lenses pad printed with the dye composition described in example 2 containing approximately 7% dye-1 and 93% by weight clear base compared to lenses pad printed without the dye composition. Formulation a of table 2 was dispensed in a pad printing die. Using high intensity (8 mW/cm)²) And low intensity (4 mW/cm)²) Curing the lenses were cured for comparison.

The experiment was carried out as follows: the pad printing is closed and the lens mold containing the monomer mixture is placed in a curing tunnel. Once the tunnel is full, the machine is stopped completely, and the pallets of each row are removed from the tunnel, marked with their positions. The position of the tray corresponds to the amount of light to which the lens is exposed during this process. This process was repeated until the desired amount of sample was collected for each monomer mixture and light intensity tested. The results are shown in fig. 8A and 8B.

Example 11

The photopolymerization of formulation C listed in Table 2 was monitored using an ATS StressTech rheometer (available from ATS Rheosystems Inc., address: 52 Georgeotown Road, Bordentown, N J08505) equipped with a photocuring attachment comprising a temperature control cell having a quartz lower plate and an aluminum upper plate, and an OmniCure mercury arc lamp (available from EXFO Photonic solutions Inc., address: 2260 Argentia Rd., Mississauga, ON L5N 6H7 CANADA) having a bandpass filter (available from Andove corporation, address: 4 Commercial Drive, em, NH 03079 Sal 2800 USA) located below the quartz plate. Adjusting the intensity of the radiation to 4.5 +/-0.5 mW/cm²The radiation intensity was measured using an IL1400A radiometer and an XRL140A sensor (International Light, Inc. at Address: 17 Graf Road, Newburyport, MA 01950) were measured on the surface of a quartz window. The temperature is controlled at 60.0 +/-0.1 ℃.

After approximately 0.25mL of the reactive monomer mixture was placed on the lower plate of the rheometer, the 25mm diameter upper plate was lowered to 0.500 ± 0.001mm above the lower plate and held until the reaction reached the gelation point. The reaction starts by turning on OmniCure after the sample is allowed to reach thermal equilibrium (-5 minutes, determined by the plateau in steady shear viscosity during sample warming). During this time, the sample chamber was purged with nitrogen at 400sccm while the sample was in thermal equilibrium. After this initial purge, with CheckPoint O₂The sensor (PBI Dansensor, available from Topac, Inc.; address: 101 Derby St., #203 Hingham, MA 02043) monitored the oxygen level in the sample chamber at 0.5. + -. 0.1%. During the reaction, the rheometer continuously monitored the strain induced by the applied dynamic stress (fast oscillatory mode), where the strain at the applied sinusoidal stress (applied at a frequency of 1.0 Hz) was measured using a time period of less than a full cycle. The dynamic shear modulus (G'), loss modulus (G ") and gap height were monitored as a function of exposure time. As the reaction proceeds, the shear modulus is increased from<1Pa increase to>0.1Mpa, tan δ (= G "/G') decreases from almost infinity to less than 1. For many reactive crosslinking systems, the gelation point is defined as the point in time when tan δ = 1 (the cross-over point when G' = G "). At the point in time when G' reached 100Pa (shortly after the gelation point), the restriction of the upper plate by the gap height (self-tension mode: tension = 0) was removed so that the gap between the upper and lower plates would change as the reactive monomer mixture shrinks during curing and the stress due to shrinkage was kept at a minimum. The measurement of the change in gap provides an estimate of the amount of shrinkage caused by the polymerization reaction. After 10 minutes of exposure, OmniCure was turned off (i.e., the cure was terminated).

The results are shown in fig. 9-11, which show the difference in gelation point and time to 95% conversion between lenses made with the same initiator but different filters and photochromic dye concentrations. As can be seen by comparing fig. 9B, 10B, and 11B, in which the development of modulus (G' versus time) of the various polymers prepared in example 11 is shown, the efficiency of conversion is improved when using a filter that blocks wavelengths where the photochromic dye exhibits absorbance.

While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention to adapt the particular situation. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope and spirit of the appended claims.

Claims (17)

1. A method of manufacturing a contact lens comprising at least one photochromic compound, said method comprising the steps of:

selecting a photoinitiator that absorbs at a first wavelength;

selecting a photochromic dye that exhibits substantial absorption at a first wavelength when the dye is at a first temperature, but is in an unactivated state at a second temperature;

dispensing into a mold a reaction mixture comprising at least one polymerizable monomer, a photoinitiator, and a photochromic compound;

warming the reaction mixture to the second temperature to maintain the photochromic compound in an unactivated state at the first wavelength;

curing the reaction mixture at the second temperature to form a photochromic contact lens by exposing the mixture to radiation comprising the first wavelength,

wherein the photochromic compound is a polymerizable photochromic dye that is copolymerized with at least one polymerizable monomer in the step of curing the reaction mixture.

2. The method of claim 1, wherein the radiation is provided by a light emitting diode.

3. The method of claim 1, wherein the radiation omits at least a portion of the wavelength absorbed by the photochromic compound in an unactivated state.

4. The method of claim 1, wherein the radiation omits all wavelengths absorbed by the photochromic compound in an unactivated state.

5. The method of claim 1, wherein the first temperature is about 25 ℃ and the second temperature is at least 40 ℃.

6. A method of making a photochromic contact lens, comprising the steps of:

selecting a photoinitiator that absorbs at a first wavelength within 380nm to 780 nm;

selecting a photochromic dye that exhibits substantial absorption at the first wavelength when at a temperature of 25 ℃, but which is in an unactivated state at the first wavelength when at a temperature of 70 ℃;

disposing a reaction mixture on a mold, the mixture comprising at least one polymerizable siloxane monomer, a photoinitiator, and a photochromic dye;

warming the reaction mixture to a temperature between 40 ℃ and 90 ℃ to maintain the photochromic compound in an unactivated state at the first wavelength;

forming a photochromic contact lens material by curing the warmed reaction mixture by irradiating the mixture with light comprising said first wavelength,

wherein the photochromic compound is a polymerizable photochromic dye that is copolymerized with at least one polymerizable monomer in the step of curing the reaction mixture.

7. The method of claim 1 or 6, wherein the photochromic compound is uniformly dispersed throughout the contact lens.

8. The method of claim 1 or 6, wherein the photochromic compound is disposed in a central circular area of 1 to 9mm in diameter, thereby forming a contact lens only in the pupillary region, said central circular area being centered at the geometric center of the contact lens and said central circular area being surrounded by an area free of the photochromic dye.

9. The method of claim 1 or 6, wherein the first wavelength is between 400nm and 500 nm.

10. The method of claim 1 or 6, wherein the first wavelength is between 420nm and 480 nm.

11. The method of claim 1 or 6, wherein the temperature of the warming step is between 55 ℃ and 75 ℃.

12. The method of claim 1 or 6, wherein the temperature of the warming step is between 60 ℃ and 70 ℃.

13. The method of claim 1 or 6, wherein the mold is exposed to radiation from the top and bottom sides of the mold.

14. The method of claim 13, wherein the radiation is balanced from the top and bottom sides of the mold.

15. The method of claim 1 or 6, wherein the curing step further comprises filtering wavelengths outside the range of 400nm to 420 nm.

16. The method of claim 1 or 6, wherein the curing step further comprises filtering wavelengths outside the range of 420nm to 440 nm.

17. The method of claim 6, wherein the illumination is provided by light emitting diodes.