MXPA00011034A - Method for polymerizing contact lenses having uv absorbing properties - Google Patents

Abstract

A method for preparing a lens having UV-absorbing properties involves charging to a mold a monomer mixture comprising lens-forming monomers and an essentially non-UV-absorbing compound;exposing the monomer mixture in the mold to a light source including ultraviolet light to cure the monomer mixture and form the lens, whereby the non-UV-absorbing compound converts to a UV-absorbing agent.

Description

METHOD FOR POLYMERIZING CONTACT LENSES THAT HAVE PROPERTIES OF UV ABSORPTION BACKGROUND OF THE INVENTION The present invention relates to a method of preparing contact lenses that contain an ultraviolet absorbing agent and which are capable of absorbing UV radiation, where the mixture of lens-forming monomers is cured by exposure to the UV light. Lenses, such as contact lenses or intraocular lenses, can include a UV absorbing agent in the lens to absorb light in the ultraviolet region of the spectrum, more specifically to absorb light in the region of approximately 200 to 400 nm and , especially, from about 290 to 400 nm. Representative UV absorbent materials are described for such lens applications in US Pat. Nos. 4,304,895 (Loshae), 4,528,311 (Beard et al.) And 4,719,248 (Bambury et al.). In general, such lenses are formed by free radical polymerization of a monomer mixture that includes the desired lens-forming monomers, usually in the presence of heat (thermal polymerization) or a light source (photopolymerization). A particular method for producing contact lenses involves the thermal polymerization of the initial monomer mixture in tubes in a heated water bath to obtain rod-shaped articles, the rods of which are then cut into buttons, the buttons being turned into contact lenses; said methods for forming lenses that include a UV absorbing agent are illustrated in U.S. Pat. aforementioned Nos. 4,304,895 (Los-haek) and 4,528,311 (Beard et al.). Other methods involve casting the lenses directly into molds, where the monomer mixture is loaded into the mold and polymerized by exposure to ultraviolet radiation. In case it is desired to form lenses by a photopolymerization process, the UV curing (ie, the exposure of the monomer mixture to radiation purely in the ultraviolet region) of the monomer mixtures has been shown be very effective It is also possible to perform the photopolymerization using a light source which also includes light in the visible region of the spectrum, although light in this region is generally less effective in effecting the polymerization of conventional lens-forming monomer mixtures than UV cured However, for lenses that include a UV absorbing agent, problems arise when trying to cure the monomer mixtures, as this agent absorbs UV light, thus decreasing the amount of UV light available to effect the polymerization and resulting in an effective or non-homogeneous cure of the monomer mixture. EP-0 188 110-A1 discloses hydrogel-forming polymers for contact lenses and lens lenses that can include a UV absorber. One class of UV absorbing agents is that of polyunsaturated resins containing phenyl terephthalate and phenyl isophthalate, which undergo redistribution of Fries when exposed to UV radiation to form 2-hydroxybenzophenone, which works as a rest of UV absorption in the redistributed form. U.S. Pat. No. 5,141,990 discloses acrylic photocurable compositions that include a polymerizable precursor, such as 2-acetoxy? -5-v? N? Lfen? Lbenzot? Azole, where the residue 2-acetox? is it regenerated as a 2-h? drox group? to form a UV absorbing chromophore. Accordingly, it would be desirable to provide a method by which the lenses that exhibit effective UV-absorbing properties can be polished by conventional methods of photopolymerization of free radicals. The present invention provides said method and solves the aforementioned problems SUMMARY OF THE INVENTION This invention provides a method for preparing a lens having UV absorbing properties, consistent in loading into a mold a monomer mixture consisting of lens-forming monomers and an essentially non-UV absorbing compound., exposing the monomer mixture to a light source that includes ultraviolet light to cure the monomer mixture and form the lens, whereby the essentially non-UV absorbing compound is converted to a UV absorbing agent. Preferably, the lens is a contact lens or an intraocular lens, more preferably a hydrogel contact lens. Preferred compounds included in the monomer mixture and which are essentially non-UV absorbent, but capable of becoming a UV absorbing agent, are compounds of the formula: wherein each of R10, R11 and R12 are independently hydrogen or a substituent and R15 is a protective radical which makes the compound essentially non-UV absorbent. Especially preferred are compounds of this formula wherein at least one of R 11 and R 12 is an ethylenically unsaturated radical of the formula -R 13 -X-CO-C (R 14) = CH 2, where R 13 is a single bond or C 1 alkylene C10, X is -0- or -NH- and R14 is hydrogen or methyl, and compounds where -OR15 is -OS02C6H5. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The monomer mixtures employed in the invention include conventional lens-forming monomers. Lens-forming monomers are monomers which are polymerizable by free radical polymerization, which generally includes an activated unsaturated radical and, more preferably, an ethylenically unsaturated radical. (As used herein, the term "monomer" represents relatively low molecular weight compounds] which are polymeraseable by polymerization of free radicals, as well as higher molecular weight compounds which are polymerizable by polymerization of free radicals and which are also referred to as "prepolymers", "macromonomers" and related terms). A particularly preferred class of materials are hydrogel copolymers. A hydrogel is a crosslinked polymer system that can absorb and retain water in a state of equilibrium. Accordingly, for hydrogels, the monomer mixture will typically include at least one hydrophilic monomer and a crosslinking agent (a crosslinker being defined as a monomer having multiple polymerizable functionalities). Suitable hydrophilic monomers include: unsaturated carboxylic acids, such as methacrylic and acrylic acids, acrylic-substituted alcohols, such as 2-hydroxyl methacrylate and 2-hydroxy acyl-to-hydroxyl. ? ethanol, vmil-lactams, such as N-vinylpyrroli-dona, and acrylamides, such as metac? lamide and N, Nd? met? lacr? lam? da. Typical crosslinking agents include polymers, typically di- or t-vimic monomers, such as di- or tri (meth) acrylates of diethylene glycol, triethylene glycol, butylene glycol and hexane-1,6-diol; divimlben- Ceno, and others known in the art. Another preferred class of lens-forming monomers are those that form silicone hydrogel copolymers. Such systems include, in addition to a hydrophilic monomer, a silicone-containing monomer. A suitable class of silicone-containing monomers includes monofunctional and bulky polysiloxane alkyl monomers represented by Formula (I): where: X represents -COO-, -CONR4-, -OCOO- or -OCONR4-, where each R4 is H or lower alkyl, R3 represents hydrogen or methyl, h is 1 to 10 and each R2 represents more preferably an alkyl radical lower or halogenated alkyl, a phenyl radical or a radical of the formula -S? (R5) 3 wherein each R5 is independently a lower alkyl radical or a phenyl radical. Such bulky monomers specifically include metac? Loxipropyl? S (trimethylsilyloxy) silane, pentamethyldisiloxane methyl methacrylate, tris (t? Methylsiloxy) methacryloxypropyl silane, methyl di (tr? Met? S? Lox?) Metac? Lox? Met? ls? lane, 3- [tris (t? methyloxy) silyl] propylvlyl carbamate and 3- [t? s (t? methylsiloxy) s? l?] propylene carbonate. Another suitable class is the multifunctional monomers containing siloxane ethylenically "endcapped", especially the difunctional monomers represented by Formula (II) .- (?) where: each A 'is independently an activated msatured group, each R' is independently an alkylene group from 1 to 10 carbon atoms, where the carbon atoms may include ether, urethane or ureido bonds between them; each R8 is independently selected from monovalent hydrocarbon radicals or halogen-substituted monovalent hydrocarbon radicals having from 1 to 18 carbon atoms and which may include ether linkages therebetween, and a is an integer equal to or greater than 1. Preferably, each R8 is independently selected from alkyl groups, phenyl groups and fluoro-substituted alkyl groups. It is further noted that at least one R8 may be a fluoro-substituted alkyl group, such as that represented by the formula: -D'- (CF2) gM 'where: D' is an alkylene group of 1 to 10 carbon atoms , wherein said carbon atoms may include ether linkages therebetween; M 'is hydrogen, fluorine or an alkyl group, but preferably hydrogen, and s is an integer from 1 to 20, preferably from 1 to 5. With respect to A', the term "activated" is used.

This is to describe more saturated groups that include at least one substituent that facilitates the polymerization of free radicals, preferably an ethylenically unsaturated radical. Although a wide variety of such groups can be used, preferably A 'is an ester or amide of (meth) acrylic acid represented by the general formula: wherein X is preferably hydrogen or methyl and Y is -0- or -NH-. Examples of other suitable activated, unsaturated groups include vilcarbonates, vilcarbamates, fumara-tos, fumaramides, maleates, acyolithium, vinyl ether and styloyl. Specific examples of monomers of Formula (II) include the following: where: d, f, g and k vary between 0 and 250, preferably between 2 and 100; h is an integer from 1 to 20, preferably from 1 to 6, and M 'is hydrogen or fluorine. Other monomers containing silicone include the silicone-containing monomers described in US Patents. No. 5,034,461, 5,610,252 and 5,496,871, the descriptions of which are hereby incorporated by reference. In the Many other silicone-containing monomers are known. As indicated, the polymerization (or cure) of monomer mixtures to form lenses by exposure of the monomer mixture to ultraviolet radiation has been shown to be very effective, however, for lenses which include a UV absorbing agent, problems arise when attempting to perform the polymerization of the monomer mixture by exposure to radiation, since this agent absorbs UV light. The invention provides a method by which lenses with UV-absorbing properties can be prepared. by conventional methods involving free radical polymerization induced by UV light More specifically, a compound which is essentially non-UV absorbent, but which can be converted into a non-UV absorbent, is then added to the monomer mixture comprising the lens-forming monomers. a UV absorbing agent in a post-polymerization process, that is, after curing the lens, for example, having been photopolymerized by UV curing As used herein, the term "UV absorbing agent" refers to an agent which, when incorporated into a film of the lens-forming monomers having a thickness of 0.02 mm, it is able to reduce the transmittance of light in the region of 320 to 400 nm to at least 50 percent of a similar sample lacking UV absorbing agent and, preferably, at least 70 percent, more preferably at least 85 percent. It is also preferred that said sample incorporating the UV absorbing agent transmit no more than 70% of the light in the region of 320 to 400 nm and no more than 90% of the light in the region of 290 to 320 nm. The term "essentially non-UV absorbing agent" represents an agent which, if incorporated into said film sample, is capable of reducing the transmittance of light in the region from 320 to 400 nm to no more than 40 100 percent of a similar sample that lacks this agent (and, preferably, no more than 20 percent). A preferred class of known UV absorbing agents for contact lens and infra-ocular lens applications includes benzothiazoles containing a phenol moiety. Examples of said benzothiazoles are described in U.S. Pat. No. 4,528,311 (Beard et al.), 4,716,234 (Dunks et al.), 4,719,248 (Bambury et al.), 3,159,646 (Milio-nis et al.) And 3,761,272 (Manneus et al.). col.), whose descriptions are here incorporated by way of reference. Specific examples include 2- (2 '-h? Drox? -5' -metac? Lamidophenyl) -5-chlorobenzotriazole, 2- (2'-hydrox? -5 '-metac? Lamidophenyl) -5- methoxybenzot? a-zol, 2 - (2'-h? drox? -5 '-metac? lox? prop? l -3' -t-butylphenyl) -5-chlorobenzot? azole, 2 - (2'-h? drox? -5 '-methacryloxyethyl-nil) benzot? azole and 2- (2'-hydrox? -5' -metac? loxipropylfe-nyl) benzot? azole. These benzothiazoles can be represented by the general formula (I): wherein R10 may be hydrogen or a substituent (representative substituents being selected from the group consisting of halogen, C1.-C4 alkyl and C? -C alkoxy) and each of R11 and R12 may independently be hydrogen or a substituent (being selected representative substituents among the group consisting of halogen, C 1 -C 4 alkyl and C 1 -C 4 alkoxy). Preferably, at least one of R11 or R12 is a more ethylenically polymerizable ethylenically moiety, such as -R13-X-CO-C (R14) = CH2 where R13 is a single bond or C1-C10 alkylene, X is -O- or - NH- and R14 is hydrogen or methyl.

The essentially non-UV-absorbing agent which is actually incorporated into the initial monomer mixture, together with the lens-forming monomers, is a derivative of the UV-absorbing agent where the hydroxyl radical of the fe-nol moiety is substituted with a protecting group, whose group The protector makes the agent essentially non-UV absorbing (ie, the protecting group essentially changes the absorption properties of the compound, so that the agent does not absorb so strongly in the range of 320 to 400 nm). After exposure to UV light, UV light acts as a catalyst for a photo-Fries redistribution, where the hydroxyl residue is regenerated to give a UV absorbing agent. For the preferred benzothiazoles, the agents which are derivatives of the compounds of Formula (I) and which are added to the initial mixture of monomers can be represented by the general formula (la): where R, R and R have the same meanings as for the Formula (I) and R is the protective group that rearranges after exposure to UV light. As in Formula (I), preferably at least one of R11 or R12 in Formula (la) is a polymerizable ethylenically unsaturated residue, such as -R13-X-CO-C (R14) = CH2 A specific example of the radical - OR15, and the most preferred radical, is -OS02C6H5. The agents of Formula (Ia) can be prepared by methods generally known in the art. For example, for the most preferred protecting group, -S02C6H5, a compound of Formula (I) can react with C6H5S02C1 in the presence of triethylamine. In the following examples, a representative detailed synthesis is provided. For the preferred benzotriazoles of Formula (la), the redistribution of photo-Fries type can be illustrated as follows .- (Ib) (the) Another representative class of UV absorbing agents are the benzophenone UV absorbers which contain a phenolic radical. Specific examples are 2, 2-d? H? Drox? -4,4-dimethoxybenzophenone, 2, 2-d? H? Drox? -4-methox? Benzophenone and the polymerizable benzophenones described in US Pat. No. 4,304,895 (Loshaek), the description of which is hereby incorporated by reference. Accordingly, the derivatives of these UV absorbing agents, incorporated into the monomer mixture initially in the practice of this invention, are benzophenone derivatives in which at least one hydroxyl radical of the phenolic radical is substituted with one of the groups protectors mentioned above. Consequently, for this class of UV absorbing agents, redistribution of the photo-Fries type can be illustrated as follows: (le) (Id) the formula (le) representing the agent incorporated in the initial mixture of monomers and R11 and R12 representing the optional substituents on the benzene ring, which have a meaning as in Formula (I). Compounds of Formula (le) can be prepared from the corresponding parental UV-absorbing compounds containing phenol, for example, for compounds of Formula (Ie) containing the preferred protecting group, -S02C6H5, the benzophenone parenteral UV-absorbing compounds containing phenol can react with C6H5S02C1 in the presence of triethylamine. Especially preferred for contact lens and infra-ocular lens applications are agents that include an ethylenically unsaturated polymerizable moiety. For example, as mentioned for the benzothiazoles of Formula (la), preferred agents include those having at least one ethylenically unsaturated radical. These agents copolymerize with the lens-forming monomers, that is, that the agent is an integral part of the copo-liméca network. Surprisingly, it has been found that, even though these compounds copolymerize with the lens-forming monomers, the agents still undergo the redistribution of photo-Fries upon exposure to UV light, to render the resulting lens UV-absorbent. Agents convertible to UV absorbing agents will generally be included in the monomer mixture at about 0.1 to about 5 weight percent, more preferably at about 0.2 to about 2 weight percent. The monomer mixtures may also include a coloring agent that imparts some degree of color to the lens. Monomeric mixtures will generally include a polymerization initiator, such as commercial initiators based on acetophenone, titanocene-based initiators and / or initiators based on aromatic phosphine oxide, available under the trade names Darocur or Irgacur. In general, the monomer mixture, which contains the lens-forming monomers and the essentially non-absorbing UV protected agent, is charged into a mold and then subjected to light to effect curing of the monomer mixture in the mold. Various methods are known for cure a mixture of monomers in the production of contact lenses, including spin casting and static casting. The methods of spin casting involve loading the monomer mixture into a mold and rotating the mold in a controlled manner while exposing the monomer mixture to light. The methods of static emptying involve the loading of the monomer mixture between two sections of the mold, one section of the mold having a shape that allows to form the anterior surface of the lens and the other section of the mold having a shape that allows to form the posterior surface of the mold. the lens, and the curing of the monomer mixture by exposure to UV light. Such methods are described in U.S. Pat. Nos. 3,408,429, 3,660,545, 4,113,224, 4,197,266 and 5,271,875. The following examples illustrate various preferred embodiments. EXAMPLE 1 Synthesis of Protected Derivative of the UV Absorbing Agent of Formula (1) 2- [3- (2H-Benzotrolol-2-yl) -4-benzenesulfonyloxy benzyl] ethyl methactal To a round-bottomed flask of 1 liter equipped with a mechanical stirrer, thermometer, reflux condenser and dropper funnel are added, ba or dry nitrogen, methacrylate, 2- [3- (2H-benzoth? azol-2-? l) -4-h? drox? feml] ethyl ester (20 g, 0.062 mole), t? ethylamma (7.1 g, 0.07 mole) ) and 400 ml of chloroform. The reaction mixture is cooled to 5 ° C, at which time benzenesulfonyl chloride (12.01 g, 0.068 moles) is slowly added. After the addition is complete, the reaction is allowed to reach room temperature. Stirring is continued for two more hours. The resulting reaction solution is washed twice with 2N HCl, once with saturated saline and twice with a 5% solution of sodium bicarbonate. The organic layer is collected and dried over magnesium sulfate, filtered and placed in a rotoeva-porator to remove the chloroform. The unpurified solid protected toluene is dissolved in 30 ml of methylene chloride and passed through a column of silica gel using methylene chloride (450 ml) as eluent, followed by a 50/50 mixture. methylene chloride / ethyl acetate (450 ml). Six fractions were collected (volume of solvent approximating 150 ml / fraction) and the solvent was removed. Fractions 1 and 2 contained both starting material and product, as determined by thin layer chromatography. Fractions 3, 4, 5 and 6 contained the desired protected toluol (total yield 14 g, m.p. 86-88 ° C). The molecular structure was confirmed by "FTIR" and "^ H-NMR".

Example 2 UV spectrum data The UV spectrum of the compound prepared in Example 1 was compared to the UV spectrum of its parent compound (a compound of Formula (I)2- (2 '-h? Drox? -5' -metac? Loxietilphenyl) benzot? Azole) by diluting each compound in a solvent at a 1: 100,000 dilution ratio and measuring the amount of light absorption. While the parent compound exhibited a sharp peak of absorption at approximately 350 nm, the compound of Example 1 exhibited no such peak, having instead a well defined absorption peak at approximately 300 nm, indicating that the addition of the protecting group -OS02C6H5 was effective to significantly change the UV absorbance at a lower wavelength. Example 3 The compound of Example 1 was added at 0.8 percent by weight to a mixture of 2-hydroxyethyl metac-late monomers (MAHE), ethylene glycol dimethacrylate (DMAEG, a crosslinker), benzoin methyl ether (BME, an initiator) and glycerol (a diluent). For comparative purposes, the compound 2- (2'-h? Drox? -5 '-metacryloxyethylfem) benzot? Azole was added at 0.8 weight percent to the same base monomer mixtures. Both resulting mixtures were emptied between two glass plates and exposed to UV light (2500? / cm2) for one hour. While the sample containing the compound of Example 1 was effectively polymerized in 3 to 4 minutes to form a film, the comparative mixture, containing the conventional UV absorbing agent, failed to polymerize. Example 4 The compound of Example 1 was added at 0.4 weight percent and 0.8 weight percent to the same monomeric mixture based on MAHE described in Example 3. Both resulting mixtures were emptied between two plates. glass and exposed to UV light (2500? W / cm2) for one hour. For comparative purposes, the compound 2- (2'-hydrox? -5'-methac? Loxyethylphenyl) benzotriazole at 0.8 percent by weight was added to the same base monomer mixture, was emptied between two glass plates and it was thermally cured. Luminous transmittance was measured for each group of films. Comparison of the UV cured films with the thermally cured film indicated that the compound of Example 1 in the UV cured films had been at least partially rearranged, since their transmittance characteristics approximated those of the cured film with hot.

Many other modifications and variations of the present invention are possible for the person skilled in the art in the light of the teachings given herein. It is understood, therefore, that, within the scope of the claims, the present invention may be implemented in a manner different from that specifically described.

Claims (15)

1. A method for preparing a lens having UV absorption properties, consisting in: loading into a mold a monomer mixture consisting of lens-forming monomers and an essentially non-UV absorbing compound and exposing the mixture of monomers in the mold to a light source including ultraviolet light to cure the monomer mixture and form the lens, whereby the essentially non-UV absorbing compound is converted into a UV absorbing agent.

2. The method of claim 1, wherein the lens-forming monomers include a hydrophilic monomer and a crosslinking monomer.

The method of claim 1, wherein the lens-forming monomers include a hydrophilic monomer and a silicone-containing monomer.

4. The method of claim 1, wherein the monomer mixture includes a polymerization initiator.

5. The method of claim 1, wherein the lens is a contact lens.

6. The method of claim 5, wherein the The monomer mixture is cured in a mold cavity formed between a first mold section having a molding surface having a shape that provides a rear contact lens surface and a second mold section 5 having a molding surface that It has a shape that provides an anterior contact lens surface.

The method of claim 1, wherein the essentially non-UV absorbing compound is converted to a UV absorbing agent, such that the lens formed 10 transmits no more than 50% of the incident light at wavelengths in the region of 320 to 400 nm.

The method of claim 7, wherein the lens formed transmits no more than 70% of the light in the region of 320 to 400 nm and no more than 90% of the light in the region of 15 290 to 320 nm.

The method of claim 1, wherein the essentially non-UV absorbing compound includes an ethylenically unsaturated polymerizable radical.

The method of claim 1, wherein the essentially non-UV absorbing compound has the general formula (Ia) selected from the group consisting of halogen, C 1 -C 4 alkyl and C 1 -C 4 alkoxy, provided that at least one of R 11 and R 12 can be a polymerizable ethylenically unsaturated radical, and R 15 is a phenolic protecting radical which makes the compound essentially non-UV absorbent.

The method of claim 10, wherein at least one of R11 and R12 is an ethylenically unsaturated radical of the formula -R13-X-CO-C (R14) = CH2 where R13 is a single bond or C1-C10 alkylene, X is -O- or -NH- and R14 is hydrogen or methyl.

12. The method of claim 11, wherein R15 is -OS02C6H5.

The method of claim 11, wherein exposure to UV light converts the compound of Formula (Ia) to the following: (Ib)

14. A compound of formula: wherein each of R 10, R 11 and R 12 is independently hydrogen or a substituent selected from the group consisting of halogen, C 1 -C 4 alkyl and C 1 -C 4 alkoxy, provided that at least one of R 11 and R 12 is an ethylenically unsaturated polymerizable radical of formula -R13-X-CO-C (R14) = CH2 where R13 is a single bond or C1-C10 alkylene, X is -O- or -NH- and R14 is hydrogen or methyl, and R15 is a radical protector that makes the compound essentially non-UV absorbent.

15. A compound of formula: wherein each of R 10, R 11 and R 12 is independently hydrogen or a substituent selected from the group consisting of halogen, C 1 -C 4 alkyl and C 1 -C 4 alkoxy, provided that at least one of R 11 and R 12 is an ethylenically polymerizable radical unsaturated, and -OR15 is -OS02C6H5.