US20040186241A1 - Photochromic ocular devices - Google Patents

Abstract

Described are photochromic ocular devices such as contact lenses and intraocular lenses made of an organic polymeric material and at least one photochromic material adapted upon exposure to actinic radiation to change from a less ultraviolet radiation absorbing unactivated form to a more ultraviolet radiation absorbing activated form. The photochromic ocular device is adapted upon exposure to actinic radiation to exhibit a ratio of greater than 0.5:1.0 of increased ultraviolet radiation absorbance to increased visible radiation absorbance as measured in the Ultraviolet Photochromic Performance Test described herein.

Description

BACKGROUND OF THE INVENTION
• The present invention relates to novel ultraviolet radiation absorbing ocular devices. In particular, this invention relates to ocular devices containing photochromic materials that demonstrate an increased UV absorbance upon exposure to ultraviolet radiation present in unfiltered sunlight.[0001]
• Currently, commercially available contact lenses containing ultraviolet radiation absorbing materials are limited in their ability to block ultraviolet radiation from entering the eye. Further, such contact lenses do not meet American National Standards Institute (ANSI Z80.20-1998) Class 1 specifications for ultraviolet radiation absorption. The ANSI specifications require an average percent transmittance of less than 1 percent at 280 to 315 nanometers (nm) and less than 10 percent at 316 to 380 nm.[0002]
• In one class of contact lenses, described as hydrogels, it has been difficult to incorporate ultraviolet radiation absorbing materials into these lenses because of their hydrophilic nature and expanded structure. The majority of ultraviolet radiation absorbing materials described in the art are generally hydrophobic and have limited solubility in hydrogels. Further, if the aforementioned ultraviolet radiation absorbing materials are added in excess to the ocular device, the properties, e.g., durability, flexibility, hydrophilicity, stability to sterilizing regimes, etc., of the ocular device can be adversely effected.[0003]
• Therefore, a need remains for an ocular device that provides not only variable protection to visible light but also protection against ultraviolet radiation.[0004]
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 shows the absorption spectrum from 300 to 700 nanometers (nm) of the Example and FIG. 2 shows the absorption spectrum of the Comparative Example.[0005]
DETAILED DESCRIPTION OF THE INVENTION
• It is noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless expressly and unequivocally limited to one referent.[0006]
• For the purposes of this specification, unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and other parameters used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.[0007]
• Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.[0008]
• The phrases “at least partially curing a polymerizable composition” or “an at least partially cured polymerizable composition” refer to a polymerizable composition in which the curable or cross-linkable components are from at least partially to fully cured, crosslinked and/or reacted. In one non-limiting embodiment of the present invention, the degree of cured, crosslinked or reacted components can vary widely, e.g., from 5% to 100% of all of the possible curable, crosslinkable and/or reactable components. The term “ocular device” is defined herein to mean an ophthalmic device that physically resides in or on the eye. Nonlimiting devices can be corrective or non-corrective such as for cosmetic enhancement and include without limitation contact lenses and intraocular lenses.[0009]
• In one non-limiting embodiment, upon exposure to ultraviolet radiation, the photochromic materials described herein develop an absorbance within the ultraviolet region as well as developing an absorbance within the visible portion of the spectrum.[0010]
• In one non-limiting embodiment, the photochromic ocular device or article of the present invention comprises:[0011]
• (a) an organic polymeric material; and[0012]
• (b) at least one photochromic material adapted to change from a less radiation absorbing unactivated form to a more radiation absorbing activated form upon exposure to actinic radiation; said photochromic ocular device being[0013]
• adapted upon exposure to actinic radiation to exhibit a ratio of greater than 0.5:1.0 of increased ultraviolet radiation absorbance to increased visible radiation absorbance as measured in the Ultraviolet Photochromic Performance Test described in the Example herein. In another non-limiting embodiment, the photochromic ocular device is adapted to exhibit a ratio of at least 1.0:1.0. The ratio exhibited by the ocular device of the present invention can be any number provided that it is at least greater than 0.5:1.0, e.g., 0.8, 2, 5, 10 or 100:1.0, inclusive of the aforementioned values, e.g., 0.6:1.0 or 99:1.0.[0014]
• The aforementioned ratio is of the greatest difference between the absorbance in the unactivated and activated states in the ultraviolet spectrum (300 to 400 nm) divided by the greatest difference between the absorbance in the unactivated and activated states in the visible spectrum (400 to 700 nm) as measured in the Ultraviolet Photochromic Performance Test. The ratio is determined by plotting the spectrum of the unactivated and activated states over the wavelength range of 300 to 700 nm, measuring the greatest difference between the unactivated and activated states in both the ultraviolet and visible spectrums at the wavelengths of maximum difference and dividing the difference obtained for the ultraviolet spectrum by the difference obtained for the visible spectrum. Each of the greatest differences in the ultraviolet spectrum and visible spectrum can be determined by measuring the difference in millimeters on the plot or by the arithmetic difference in the absorbance units, although the latter method is generally an approximation.[0015]
• In one non-limiting embodiment, photochromic material (b) is chosen from naphthopyrans, e.g., 3H-naphtho[2,1-b]pyrans, 2H-naphtho[1,2-b]pyrans, indeno[2,′3,′3,4]naphtho[1,2-b]pyrans, or mixtures thereof. In another non-limiting embodiment, photochromic material (b) is chosen from 2H-naphtho[1,2-b]pyrans, indeno[2,′3,′3,4]naphtho[1,2-b]pyrans or a mixture thereof. In a further non-limiting embodiment, photochromic material (b) is chosen from indeno[2,′3,′3,4]naphtho[1,2-b]pyrans. In a series of alternate non-limiting embodiments, photochromic material (b) of the present invention includes the following naphthopyrans and/or mixtures thereof. In the definitions of the substituents shown in formulae I to III, like symbols have the same meaning unless stated otherwise.[0016]
• Alternatively, the photochromic material can be a mixture of materials represented by various mixtures of the materials represented by graphic formulae I, II or III. In one non-limiting embodiment, the naphthopyran compound can be represented by one the following graphic formulae I, II or III:[0017]

  
• In graphic formulae I, II and III, R[0018]₁, R₁′, R₂, each R3, R₄, R₅and R₆can be the group R. The R group can be represented by the following formulae IVA to IVF:
• —A  (formula IVA);
• —D—A  (formula TVB);
• —D—E—U  (formula IVC);
• —D—U—(formula IVD);
• —E—U  (formula IVE); or
• —U  (formula IVF);
• wherein —A is represented by the following formula:[0019]
• —[(OC₂H₄)_x—(OC₃H₆)_y—(OC₄H₈)_z]—J
• wherein —J is chosen from: hydroxy, (meth)acryloxy, e.g., acryloxy and methacryloxy, 2-(methacryloxy)ethylcarbamyl, epoxy, C[0020]₁-C₆alkyl, —OCH₂COOH; —OCH(CH₃)COOH; —OC(O) (CH₂)_wCOOH; —OC₆H₄SO₃H; —OC₅H₁₀SO₃H; —OC₄H₈SO₃H; —OC₃H₆SO₃H; —OC₂H₄SO₃H; or —OSO₃H; w is an integer from 1 to 18; x, y and z are each a number between 0 and 50, and the sum of x, y and z is between 1 and 50; —D— is —C(O)— or —CH₂—; —E— is represented by the following formula:
• —[(OC₂H₄)_x—(OC₃H₆) y—(OC₄H₈)_z]—
• wherein x, y and z are the same as defined for —A; —U is a residue of an organic polyol, having at least one hydroxyl group or a derivative of said residue wherein at least one hydroxyl group has been reacted to form the group J. An organic polyol residue is the remainder of the polyol after at least one hydroxyl group has been reacted.[0021]
• The group, —U, is a residue of an organic polyol which is defined herein to include hydroxylated carbohydrates discussed hereinafter. In one non-limiting embodiment, the residue is formed by the reaction of one of the hydroxyl groups on the polyol with a precursor of group —D—, such as a carboxylic acid or a methylene halide, a precursor of group —E—, such as polyalkylene glycol or a hydroxyl group as substituent R[0022]₁, R₁′, R₂, each R₃, R₄, R₅or R₆on the photochromic material (b) represented by graphic formulae I, II or III. The organic polyol can be represented by G(OH)a and the residue —U can be represented by the formula —O—G(OH)a-1, wherein G is the backbone or main chain of the polyhydroxylated compound and a is at least 2, provided that —U is not the same as —A when —J is hydroxy.
• In one non-limiting embodiment, all, none or at least one of the hydroxyls of group, —U, can be reacted to form a group represented by —J, such as a polymerizable group selected from (meth)acryloxy, 2-(methacryloxy)ethylcarbamyl, epoxy or mixtures thereof. The hydroxyl groups of —U can be reacted to form the carboxyl group containing substituent —J by methods known in the art, e.g., by Reactions B and D in allowed application Ser. No. No. 09/828,260 filed Apr. 6, 2001, to produce a carboxylated organic polyol residue. The organic polyol residue —U having the sulfo or sulfono terminating groups of —J on it can be produced by acidic condensation of the hydroxyl groups of —U with HOC[0023]₆H₄SO₃H; HOC₅H₁₀SO₃H; HOC₄H₈SO₃H; HOC₃H₆SO₃H; HOC₂H₄SO₃H; or H₂SO₄, respectively. The polymerizable groups, (meth)acryloxy, 2-(methacryloxy)ethylcarbamyl or epoxy, can be added to the polyol residue —U by condensation of the polyol with (meth)acryloyl chloride, isocyanatoethyl methacrylate or epichlorohydrin, respectively.
• Non-limiting examples of organic polyols that can be used to form the residue —U in the R group substituent of photochromic material (b) include polyols having at least 2 hydroxy groups such as (a) low molecular weight polyols, e.g., polyols having a molecular weight, i.e., the sum of the atomic weights of the constituent atoms of the polyol, that is less than 500 grams per mole, e.g., aliphatic triols, such as C[0024]₂-C₁₀aliphatic triols, polyhydric alcohols and alkoxylated low molecular weight polyols; (b) polyester polyols; (c) polyether polyols; (d) amide-containing polyols; (e) epoxy polyols; (f) polyhydric polyvinyl alcohols; (g) urethane polyols; (h) polyacrylic polyols; (i) polycarbonate polyols; and (j) mixtures of such polyols. Such polyols are known to those skilled in the art and are described in U.S. Pat. No. 6,187,444B1.
• Non-limiting examples of polyhydroxylated carbohydrates that can be used in the R group substituent of photochromic material (b) of the present invention include: low molecular weight carbohydrates of the formula C[0025]_e(H₂O)_ewherein e is from 3 to 5, e.g., aldotriose, aldoketose, erythrose, ribose, etc.; monosaccharides, e.g., simple sugars such as glucose and fructose; oligosaccharides, i.e., carbohydrates containing from two to ten monosaccharides linked together, e.g., sucrose and cyclodextrins; polysaccharides, i.e., carbohydrates containing more than ten monosaccharides linked together by glycosidic bonds, e.g., starch, cellulose, glycogen, pectin, agar, carrageenan and natural gums such as arabic and tragacanth.
• In another non-limiting embodiment, the polyhydroxylated carbohydrates described herein also include glycosides which are mono- and oligosaccharides linked to nonsugar organic compounds. A non-limiting example of which is the product of the reaction of D-glucose with ethanol to form ethyl α- & β-D-glucopyranosides. Another non-limiting class of polyhydroxylated carbohydrates are the glycoconjugates composed of glycoproteins, proteoglycans, peptidoglycans and glycolipids. Still another non-limiting class of carbohydrates includes various reaction products such as the sugar alcohols, e.g., xylitol and glucitol, produced by the reduction of mono- and oligosaccharides. A further non-limiting group of reaction products include low molecular weight carbohydrates, mono- and oligosaccharides in which one or more of the hydroxyl groups has been oxidized to a carboxylic acid functional group, or replaced by an amino group, thiol group or a halogen atom. Further information about carbohydrates that can be suitable for use in the R-group is found in the[0026]Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, 1992, Volume 4, pages 911-948.
• In another non-limiting embodiment, the —U group is a residue of polyols chosen from low molecular weight polyols or extended polyols. Non-limiting examples of such polyols include (a) glycerol, pentaerythritol and trimethylolpropane, (b) ethoxylated glycerol, ethoxylated pentaerythritol and ethoxylated trimethyolpropane; and (c) polyols (a) and (b) having at least 1 hydroxyl group reacted to produce substituent —J, a polymerizable group selected from (meth)acryloxy, 2-(methacryloxy)ethylcarbamyl or epoxy, or a mixture thereof.[0027]
• The group, —(OC[0028]₂H₄)_x—, represents poly(ethylene oxide); —(OC₃H₆)_y—, represents poly(propylene oxide); and, —(OC₄H₈)_z—, represents poly(butylene oxide). When used in combination, the poly(ethylene oxide), poly(propylene oxide) and poly(butylene oxide) groups of R can be in a random or block order within the R moiety. The letters x, y and z are each a number between 0 and 50 and the sum of x, y and z is between 1 and 50. The sum of x, y and z can be any number that falls within the range of 1 to 50, e.g., 1, 2, 3 . . . 50. The sum can also range from any lower number to any higher number within the range of 1 to 50, e.g., 6 to 50, 31 to 50. The numbers for x, y, and z are average values and can be partial numbers, eg., 9.5.
• In an alternate non-limiting embodiment, R[0029]₁is hydrogen, C₁-C₃alkyl or the group, —C(O)W, W being —OR₇, —N(R₈)R₉, piperidino or morpholino, wherein R₇is allyl, C₁-C₆alkyl, phenyl, mono(C₁-C₆)alkyl substituted phenyl, mono(C₁-C₆)alkoxy substituted phenyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl or C₁-C₆haloalkyl; R₈and R₉are each independently chosen from C₁-C₆alkyl, C₅-C₇cycloalkyl, phenyl, mono-substituted phenyl or di-substituted phenyl, said phenyl substituents being C₁-C₆alkyl or C₁-C₆alkoxy, and said halo substituent being chloro or fluoro.
• In one non-limiting embodiment, R[0030]₁′ is the group R, C₁-C₃alkyl or the group, —C(O)W, W being —OR₇, —N(R₈)R₉, piperidino or morpholino, wherein R₇is allyl, C₁-C₆alkyl, phenyl, mono(C₁-C₆)alkyl substituted phenyl, mono(C₁-C₆)alkoxy substituted phenyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl or C₁-C₆haloalkyl; R₈and R₉are each independently chosen from C₁-C₆alkyl, C₅-C₇cycloalkyl, phenyl, mono-substituted phenyl or di-substituted phenyl, said phenyl substituents being C₁-C₆alkyl or C₁-C₆alkoxy, and said halo substituent being chloro or fluoro.
• In one non-limiting embodiment, R[0031]₂is chosen from the group R, mono-R-substituted phenyl, hydrogen, C₁-C₆alkyl, C₃-C₇cycloalkyl, phenyl, mono-substituted phenyl, di-substituted phenyl, the group —OR₁₀or —OC(O)R₁₀, wherein R₁₀is C₁-C₆alkyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl, C₃-C₇cycloalkyl or mono(C₁-C₄)alkyl substituted C₃-C₇cycloalkyl, and said phenyl substituent being C₁-C₆alkyl or C₁-C₆alkoxy;
• Each R[0032]₃and each R₄are independently chosen, in one non-limiting embodiment, from the group R, hydrogen, C₁-C₆alkyl, C₃-C₇cycloalkyl, phenyl, mono-substituted phenyl, di-substituted phenyl, the group —OR₁₀or —OC(O)R₁₀, wherein R₁₀is C₁-C₆alkyl, phenyl(C₁-C₃)-alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl, C₃-C₇cycloalkyl or mono(C₁-C₄)alkyl substituted C₃-C₇cycloalkyl, and said phenyl substituent being C₁-C₆alkyl or C₁-C₆alkoxy; or each R₃and each R₄are independently a nitrogen-containing group chosen from:
• (i) —N(R[0033]₁₁)R₁₂wherein R₁₁and R₁₂are each independently chosen from hydrogen, C₁-C₈alkyl, phenyl, naphthyl, furanyl, benzofuran-2-yl, benzofuran-3-yl, thienyl, benzothien-2-yl, benzothien-3-yl, dibenzofuranyl, dibenzothienyl, benzopyridyl and fluorenyl, C₁-C₈alkylaryl, C₃-C₂₀cycloalkyl, C₄-C₂₀bicycloalkyl, C₅-C₂₀tricycloalkyl or C₁-C₂₀alkoxyalkyl, wherein said aryl group is phenyl or naphthyl or R₁₁and R₁₂come together with the nitrogen atom to form a C₃-C₂₀hetero-bicycloalkyl ring or a C₄-C₂₀hetero-tricycloalkyl ring;
• (ii) a nitrogen containing ring represented by the following graphic formula VA:[0034]

  
• wherein each Y is independently chosen for each occurrence from —CH[0035]₂—, —CH(R₁₃)—, —C(R₁₃)(R₁₃)—, —CH(aryl)—, —C(aryl)₂—, or —C(R₁₃)(aryl)—, and X is chosen from —Y—, —O—, —S—, —S(O)—, —S(O₂)—, —NH—, —N(R₁₃)— or —N(aryl)—, wherein R₁₃is C₁-C₆alkyl, said aryl is phenyl or naphthyl, m is the integer 1, 2 or 3, and p is the integer 0, 1, 2, or 3 and when p is O, X is Y;
• (iii) a group represented by one of the following graphic formulae VB or VC:[0036]

  
• wherein R[0037]₁₅, R₁₆and R₁₇are each independently chosen for each occurrence in each formula from hydrogen, C₁-C₆alkyl, phenyl or naphthyl, or the groups R₁₅and R₁₆together form a ring of 5 to 8 carbon atoms and each R₁₄is independently chosen for each occurrence in each formula from C₁-C₆alkyl, C₁-C₆alkoxy, fluoro or chloro and p is the same as defined hereinbefore;
• (iv) unsubstituted, mono- or di-substituted C[0038]₄-C₁₈spirobicyclic amine; or
• (v) unsubstituted, mono- or di-substituted C[0039]₄-C₁₈spirotricyclic amine; said substituents for (iv) and (v) are independently chosen for each occurrence from aryl, C₁-C₆alkyl, C₁-C₆alkoxy or phenyl(C₁-C₆)alkyl and n is chosen from the integers 0, 1 or 2.
• In one non-limiting embodiments, R[0040]₅and R₆together form an oxo group, a spiro-carbocyclic ring containing 3 to 6 carbon atoms or a spiro-heterocyclic group containing 1 or 2 oxygen atoms and 3 to 6 carbon atoms including the spirocarbon atom, said spiro-carbocyclic and spiro-heterocyclic groups being annellated with 0, 1 or 2 benzene rings. Examples of the spiro-carbocyclic ring substituents include spirofluoreno, spirocyclopropyl, spirocyclobutyl, spirocyclopentyl, spirocyclohexyl, spiroindan-1-yl, spiroindan-2-yl, etc. Examples of the spiro-heterocyclic group include spiroxantheno and compounds which can be represented by the expression (-0-(C₂-C₅alkanediyl)-0-), e.g., spiro-1,3-dioxolane-2, spiro-1,3-dioxane-2, etc., or spirolactones, such as butyrolactone, propiolactone, etc.
• In an alternate non-limiting embodiment, R[0041]₅and R₆are each independently the group R, hydrogen, hydroxy, C₁-C₆alkyl, C₃-C₇cycloalkyl, allyl, phenyl, mono-substituted phenyl, benzyl, mono-substituted benzyl, chloro, fluoro, the group, —C(O)X′, wherein X′ is hydroxy, C₁-C₆alkyl, C₁-C₆alkoxy, phenyl, mono-substituted phenyl, amino, mono(C₁-C₆)alkylamino, or di(C₁-C₆)alkylamino; or R₅and R6 are each independently the group, —OR₁₈wherein R₁₈is C₁-C₆alkyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl, C₃-C₇cycloalkyl, mono(C₁-C₄)alkyl substituted C₃-C₇cycloalkyl, C₁-C₆chloroalkyl, C₁-C₆fluoroalkyl, allyl, the group, —CH(R₁₉)Y′, wherein R₁₉is hydrogen or C₁-C₃alkyl and Y′ is CN, CF₃, or COOR₂₀and R₂₀is hydrogen or C₁-C₃alkyl; or R₁₈is the group, —(O)Z, wherein Z is hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy, the unsubstituted, mono-or di-substituted aryl groups phenyl or naphthyl, phenoxy, mono- or di-(C₁-C₆)alkyl substituted phenoxy, mono- or di-(C₁-C₆)alkoxy substituted phenoxy, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, phenylamino, mono- or di-(C₁-C₆)alkyl substituted phenylamino, or mono- or di-(C₁-C₆)alkoxy substituted phenylamino, each of said phenyl, benzyl and aryl group substituents being C₁-C₆alkyl or C₁-C₆alkoxy.
• The groups B and B′ are each, in one non-limiting embodiment, independently chosen from:[0042]
• (i) the unsubstituted, mono-, di- or tri-substituted aryl groups, phenyl and naphthyl;[0043]
• (ii) 9-julolidinyl or the unsubstituted, mono- or di-substituted heteroaromatic groups pyridyl, furanyl, benzofuran-2-yl, benzofuran-3-yl, thienyl, benzothien-2-yl, benzothien-3-yl, dibenzofuranyl, dibenzothienyl, carbazolyl or fluorenyl, each of said aryl and heteroaromatic substituents in (i) and (ii) being chosen from the group R, hydroxy, aryl, mono(C[0044]₁-C₆)alkoxyaryl, di(C₁-C₆)alkoxyaryl, mono(C₁-C₆)alkylaryl, di(C₁-C₆)alkylaryl, chloroaryl, fluoroaryl, C₃-C₇cycloalkylaryl, C₃-C₇cycloalkyl, C₃-C₇cycloalkyloxy, C₃-C₇cycloalkyloxy(C₁-C₆)alkyl, C₃-C₇cycloalkyloxy(C₁-C₆)alkoxy, aryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkoxy, aryloxy, aryloxy(C₁-C₆)alkyl, aryloxy(C₁-C₆)alkoxy, mono- or di-(C₁-C₆) alkylaryl(C₁-C₆)alkyl, mono- or di-(C₁-C₆) alkoxyaryl(C₁-C₆)alkyl, mono- or di-(C₁-C₆) alkylaryl(C₁-C₆)alkoxy, mono- or di-(C₁-C₆) alkoxyaryl(C₁-C₆)alkoxy, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, diarylamino, N-(C₁-C₆)alkylpiperazino, N-arylpiperazino, aziridino, indolino, piperidino, arylpiperidino, morpholino, thiomorpholino, tetrahydroquinolino, tetrahydroisoquinolino, pyrryl, C₁-C₆alkyl, C₁-C₆chloroalkyl, C₁-C₆fluoroalkyl, C₁-C₆alkoxy, mono(C₁-C₆)alkoxy(CI-C₄)alkyl, acryloxy, methacryloxy, bromo, chloro or fluoro, said aryl being phenyl or naphthyl;
• (iii) the unsubstituted or mono-substituted groups, pyrazolyl, imidazolyl, pyridyl, pyrazolinyl, imidazolinyl, pyrrolinyl, phenothiazinyl, phenoxazinyl, phenazinyl or acridinyl, each of said substituents being chosen from C[0045]₁-C₆alkyl, C₁-C₄alkoxy, phenyl, fluoro, chloro or bromo;
• (iv) monosubstituted phenyl, having a substituent at the para position that is a linking group, —(CH[0046]₂)_t— or —O—(CH₂)_t—, wherein t is the integer 1, 2, 3, 4, 5 or 6, connected to an aryl group, which is a member of another photochromic material, e.g., a naphthopyran;
• (v) the group represented by one of the following graphic formulae VIA or VIB:[0047]

  
• wherein L is carbon or oxygen and M is oxygen or substituted nitrogen, provided that when M is substituted nitrogen, L is carbon, said nitrogen substituents being chosen from hydrogen, C[0048]₁-C₆alkyl and C₂-C₆acyl; each R₂₁is C₁-C₆alkyl, C₁-C₆alkoxy, hydroxy, chloro or fluoro; R₂₂and R₂₃are each hydrogen or C₁-C₆alkyl; and q is the integer 0, 1 or 2;
• (vi) C[0049]₁-C₆alkyl, C₁-C₆chloroalkyl, C₁-C₆fluoroalkyl, C₁-C₆alkoxy(C₁-C₄)alkyl, C₃-C₆cycloalkyl, mono(C₁-C₆)alkoxy(C₃-C₆)cycloalkyl, mono(C₁-C₆)alkyl(C₃-C₆)-cycloalkyl, chloro(C₃-C₆)cycloalkyl, fluoro(C₃-C₆)cycloalkyl or C₄-C₁₂bicycloalkyl; or
• (vii) the group represented by the following graphic formula VIC:[0050]

  
• wherein P is hydrogen or C[0051]₁-C₄alkyl and Q is selected from the unsubstituted, mono-, and di-substituted members of the group consisting of naphthyl, phenyl, furanyl and thienyl, each of said group substituents being C₁-C₄alkyl, C₁-C₄alkoxy, fluoro or chloro.
• Alternatively, B and B′ taken together can form fluoren-9-ylidene, mono-, or di-substituted fluoren-9-ylidene or form a member chosen from saturated C[0052]₃-C₁₂spiro-monocyclic hydrocarbon rings, e.g., cyclopropylidene, cyclobutylidene, cyclopentylidene, cyclohexylidene, cycloheptylidene, cyclooctylidene, cyclononylidene, cyclodecylidene cycloundecylidene, and cyclododecylidene, saturated C₇-C₁₂spiro-bicyclic hydrocarbon rings, e.g., bicyclo[2.2.1]heptylidene, i.e., norbornylidene, 1,7,7-trimethyl bicyclo[2.2.1]heptylidene, i.e., bornylidene, bicyclo[3.2.1]octylidene, bicyclo[3.3.1]nonan-9-ylidene, bicyclo[4.3.2]undecane, or saturated C₇-C₁₂spiro-tricyclic hydrocarbon rings, e.g., tricyclo[2.2.1.0^2,6]heptylidene, tricyclo[3.3.1.1^3,7]decylidene, i.e., adamantylidene, and tricyclo[5.3.1.1^2,6]dodecylidene, each of said fluoren-9-ylidene substituents being chosen from C₁-C₄alkyl, C₁-C₄alkoxy, fluoro or chloro.
• In one non-limiting embodiment, there can be 0 or 1 R group or mono-R-substituted phenyl group on the photochromic material. In another non-limiting embodiment, there is at least one R group or mono-R-substituted phenyl on the photochromic material. For example, the number of R groups (including the mono-R-substituted phenyl) can be 2, 3, 4, 5 or a number equal to the total number of substituents possible on the photochromic material. When there is more than one R group or mono-R-substituted phenyl on the photochromic material, the R groups can be the same or different, e.g., there can be two different groups selected from formulae IVA to IVF.[0053]
• In another non-limiting embodiment, the photochromic material (b) of the present invention is represented by graphic formula I or III, the R group is represented by formulae: IVA, IVB, TVE or IVF; R[0054]₁′ is the group R, or R₁′ is the group, C(O)W, W being —OR₇or —N(R₈)R₉, wherein R₇is C₁-C₄alkyl, phenyl, mono(C₂-C₄)alkyl substituted phenyl, mono(C₁-C₄)alkoxy substituted phenyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkyl substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkoxy substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄) alkoxy(C₂-C₃)alkyl or C₁-C₄haloalkyl; R₈and R₉are each chosen independently from C₁-C₄alkyl, C₅-C₇cycloalkyl, phenyl, mono- or di-substituted phenyl, said phenyl substituents being C₁-C₄alkyl or C₁-C₄alkoxy, and said halo substituents being chloro or fluoro. In a further non-limiting embodiment, R₁′ is the group R or the group, —C(O)W, wherein W is the group, —OR₇, and R₇is a C₁-C₃alkyl.
• In another non-limiting embodiment, R[0055]₂is chosen from the group R, mono-R-substituted phenyl, hydrogen, C₁-C₃alkyl, C₃-C₅cycloalkyl, phenyl, mono- or di-substituted phenyl or the group —OR₁₀, wherein R₁₀is C₁-C₄alkyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkyl substituted phenyl(C₁-C₂) alkyl, mono(C₁-C₄)alkoxy substituted phenyl(C₁-C₂)alkyl, C₁-C₄alkoxy(C₂-C₄)alkyl, C₅-C₇cycloalkyl or mono(C₁-C₃)alkyl substituted C₃-C₇cycloalkyl, and the phenyl substituents are C₁-C₃alkyl or C₁-C₃alkoxy. In a further non-limiting embodiment, R₂is chosen from hydrogen, the group R, mono-R-substituted phenyl, C₁-C₃alkyl, phenyl, mono- or di-substituted phenyl or the group —OR₁₀, wherein R₁₀is C₁-C₃alkyl and said phenyl substituents are methyl or methoxy.
• In another non-limiting embodiment, each R[0056]₃is chosen from the group R or the group —OR₁₀, wherein R₁₀is C₁-C₄alkyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkyl substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkoxy substituted phenyl(C₁-C₂)alkyl, C₁-C₄alkoxy(C₂-C₄)alkyl, C₅-C₇cycloalkyl or mono(C₁-C₃)alkyl substituted C₅-C₇cycloalkyl, and the phenyl substituents are C₁-C₃alkyl or C₁-C₃alkoxy.
• In an alternate non-limiting embodiment, each R[0057]₃is independently chosen from a nitrogen-containing group comprising:
• (i) —N(R[0058]₁₁)R₁₂, R₁₁and R₁₂each being independently chosen from C₁-C₆alkyl or phenyl;
• (ii) a nitrogen containing ring represented by the graphic formula VA wherein each Y being —CH[0059]₂— and X being independently chosen from —Y—, —O—, —S—, —N(R₁₃)— and —N(phenyl)—, R₁₃being C₁-C₆alkyl, m being chosen from the integer 1, 2 or 3, and p being chosen from the integer 0, 1, 2 or 3;
• (iii) a group represented by one of graphic formulae VB or VC wherein R[0060]₁₅, R₁₆and R₁₇each being independently chosen from hydrogen or C₁-C₅alkyl, R₁₄being independently chosen from hydrogen, C₁-C₄alkyl, C₁-₄alkoxy, fluoro or chloro;
• (iv) unsubstituted or mono-substituted C[0061]₅-C₁₈spirobicyclic amine; or
• (v) unsubstituted or mono-substituted C[0062]₅-C₁₈spirotricyclic amine; said substituents for (c)(iv) and (v) are independently chosen for each occurrence from phenyl, C₁-C₆alkyl or C₁-C₆alkoxy and n being chosen from the integer 1 or 2.
• In another non-limiting embodiment, R[0063]₅and R₆are each chosen from the group R, hydrogen, hydroxy, C₁-C₄alkyl, C₃-C₆cycloalkyl, chloro, fluoro or the group, —OR₁₈, wherein R₁₈is C₁-C₃alkyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₃)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₃)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₃alkoxy(C₂-C₄)alkyl, C₁-C₃chloroalkyl, C₁-C₃fluorbalkyl, or the group, —CH(R₁₉)Y′, wherein R₁₉is hydrogen or C₁-C₂alkyl and Y′ is CN or COOR₂₀, R₂₀being hydrogen or C₁-C₂alkyl, or R₁₈is the group, —C(O)Z, wherein Z is hydrogen, C₁-C₃alkyl, C₁-C₃alkoxy, phenyl, naphthyl, the mono-substituted aryl groups, phenyl or naphthyl, phenoxy, mono- or di-(C₁-C₃)alkyl substituted phenoxy, mono- or di-(C₁-C₃)alkoxy substituted phenoxy, mono(C₁-C₃)alkylamino, phenylamino, mono- or di-(C₁-C₃)alkyl substituted phenylamino, or mono- or di-(C₁-C₃)alkoxy substituted phenylamino, each of said aryl group substituents being independently chosen from C₁-C₃alkyl or C₁-C₃alkoxy.
• In another non-limiting embodiment, B and B′ are each independently chosen from: phenyl, mono-substituted or di-substituted phenyl, each of said phenyl substituents being independently chosen from the group R, hydroxy, aryl, arlyoxy, aryl(C[0064]₁-C₃)alkyl, amino, mono(C₁-C₃)alkylamino, di(C₁-C₃)alkylamino, N-(C₁-C₃)alkylpiperazino, indolino, piperidino, morpholino, pyrryl, C₁-C₃alkyl, C₁-C₃chloroalkyl, C₁-C₃fluoroalkyl, C₁-C₃alkoxy, mono(C₁-C₃)alkoxy(C₁-C₃)alkyl, chloro or fluoro; the groups represented by graphic formulae VIA and VIB wherein L is carbon and M is oxygen, R₂₁is C₁-C₃alkyl or C₁-C₃alkoxy, R₂₂and R₂₃are each hydrogen or C₁-C₄alkyl and q is 0 or 1; C₁-C₄alkyl; or the group represented by graphic formula VIC, wherein P is hydrogen or methyl and Q is phenyl or mono-substituted phenyl, said phenyl substituent being C₁-C₃alkyl, C₁-C₃alkoxy or fluoro; or B and B′ taken together form fluoren-9-ylidene, mono-substituted fluoren-9-ylidene or a member chosen from saturated C₃-C₈spiro-monocyclic hydrocarbon rings, saturated C₇-C₁₀spiro-bicyclic hydrocarbon rings, or saturated C₇-C₁₀spiro-tricyclic hydrocarbon rings, said fluoren-9-ylidene substituent being chosen from C₁-C₃alkyl, C₁-C₃alkoxy, fluoro or chloro.
• In a further non-limiting embodiment, photochromic material (b) is represented by graphic formula III, each R[0065]₃is the group R represented by formula IVE or IVF, or the group —-OR₁₀, wherein R₁₀is C₁-C₃alkyl; or each R₃is chosen from:
• (i) —N(R[0066]₁₁)R₁₂, R₁₁and R₁₂each being C₁-C₃alkyl;
• (ii) a nitrogen containing ring represented by graphic formula VA wherein each Y for each occurrence being —CH[0067]₂— and X being independently chosen from —Y—, —O—, and —N(R₁₃)—, R₁₃being C₁-C₄alkyl, m being chosen from the integer 1 or 2, and p being chosen from the integer 0, 1 or 2; or
• (iii) a group represented by graphic formulae VC or VB wherein R[0068]₁₅, R₁₆, and R₁₇each being hydrogen and n is 1 or 2.
• R[0069]₅and R₆are each the group R, hydrogen, hydroxy, C₁-C₄alkyl or the group —OR₁₈, wherein R₁₈is C₁-C₃alkyl. B and B′ are each independently chosen from: phenyl, mono- or di-substituted phenyl, preferably substituted, in one non-limiting embodiment, in the meta and/or para positions; each of said phenyl substituents being chosen from the group R, hydroxy, C₁-C₃alkyl, C₁-C₃alkoxy, phenyl, piperidino, morpholino, fluoro or chloro; or B and B′ taken together form fluoren-9-ylidene, adamantylidene, bornylidene, norbornylidene, or bicyclo[3.3.1]nonan-9-ylidene.
• In a still further non-limiting embodiment, photochromic material (b) is chosen from:[0070]
• (a) 3-(4-methoxyphenyl)-3-phenyl-6,11-dimethoxy-13-methyl-13-(2-{2-[N-(2-methacryloxyethyl)carbamoyloxy]ethoxy}ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;[0071]
• (b) 3-(4-methoxyphenyl)-3-phenyl-6,11-dimethoxy-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)—3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;[0072]
• (c) 3,3-diphenyl-6,7-dimethoxy-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]-naphtho[1,2-b]pyran;[0073]
• (d) 3-(4-methoxyphenyl)-3-(2,4-dimethoxyphenyl-6,11-dimethoxy-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;[0074]
• (e) 3-(4-methoxyphenyl)-3-phenyl-6-methoxy-7-morpholino-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;[0075]
• (f) 3,3-diphenyl-6,7,10,11-tetramethoxy-13-ethyl-13-(2-{2-[N-(2-methacryloxyethyl)carbamoylohoxy}ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;[0076]
• (g) 2,2-diphenyl-5-(2-(2-(2-methacryloxyethyl)ethoxy) ethoxy)carbonyl-9-methoxy-2H-naphtho[1,2-b]pyran;[0077]
• (h) 2,2-di(4-fluorophenyl)-5-(2-(2-(2-methacryloxy-ethyl)ethoxy)ethoxy)carbonyl-6-phenyl-9-methoxy-2H-naphtho[1,2-b]pyran;[0078]
• (i) 2,2-diphenyl-5-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)carbonyl-8,9-dimethoxy-2H-naphtho[1,2-b]pyran; or[0079]
• (j) mixtures thereof.[0080]
• The materials represented by graphic formulae I, II or III can be produced by methods known to those skilled in the art. For example, the materials represented by graphic formula I can be produced by methods disclosed in U.S. Pat. No. 5,458,814 at column 2, line 18 to column 9, line 5; U.S. Pat. No. 5,573,712 at column 2, line 19 to column 8, line 64; U.S. Pat. No. 5,650,098 at column 2, line 7 to column 9, line 52; and U.S. Pat. No. 5,651,923 at column 2, line 11 to column 14, line 62; the materials represented by graphic formula II can be produced by methods disclosed in U.S. Pat. No. 5,466,398 at column 2, line 19 to column 10, line 30; U.S. Pat. No. 5,578,252 at column 2, line 19 to column 9, line 40; 5,637,262 at column 2, line 23 to column 10, line 37; the materials represented by graphic formula III can be produced by the methods disclosed in U.S. patent application Ser. No. ______filed even date herewith on Mar. 20, 2003: and the materials represented by graphic formula I, II and III can be produced by methods described in U.S. Pat. No. 6,113,814 at column 2, line 24 to column 23, line 29 and allowed U.S. patent application Ser. No. 09/828,260 filed Apr. 6, 2001, which disclosures are incorporated herein by reference.[0081]
• Non-limiting examples of photochromic materials (b) represented by graphic formulae I-III or a mixture thereof can be used in various ocular devices such as contact lenses that either have or do not have prescribed refractive and/or prismatic powers, haptic (scleral) contact lenses as well as flexible paralimbal contact lenses and intraocular lenses such as intracorneal lenses. Such lenses are described in ANSI Z80.20-1998 American National Standard for Ophthalmics—Contact Lenses—Standard Terminology, Tolerances, Measurements and Physicochemical Properties.[0082]
• In one non-limiting embodiment, it is contemplated that photochromic material (b) of the present invention can be used alone or in combination with other such materials of the present invention, or in combination with one or more other organic photochromic materials (c), e.g., photochromic materials having at least one activated absorption maxima within the range of between about 400 and 700 nanometers.[0083]
• In another non-limiting embodiment, photochromic material (c) can include the following classes of materials: chromenes, e.g., naphthopyrans, benzopyrans, indenonaphthopyrans, phenanthropyrans or mixtures thereof; spiropyrans, e.g., spiro(benzindoline)naphthopyrans, spiro(indoline)benzopyrans, spiro(indoline)naphthopyrans, spiro(indoline)quinopyrans and spiro(indoline)pyrans; oxazines, e.g., spiro(indoline)naphthoxazines, spiro(indoline)pyridobenzoxazines, spiro(benzindoline)pyridobenzoxazines, spiro(benzindoline)naphthoxazines and spiro(indoline)benzoxazines; mercury dithizonates, fulgides, fulgimides and mixtures of such photochromic compounds.[0084]
• Such photochromic materials and complementary photochromic materials are described in U.S. Pat. No. 4,931,220 at column 8, line 52 to column 22, line 40; U.S. Pat. No. 5,645,767 at column 1, line 10 to column 12, line 57; U.S. Pat. No. 5,658,501 at column 1, line 64 to column 13, line 17; U.S. Pat. No. 6,153,126 at column 2, line 18 to column 8, line 60; U.S. Pat. No. 6,296,785 at column 2, line 47 to column 31, line 5; U.S. Pat. No. 6,348,604 at column 3, line 26 to column 17, line 15; and U.S. Pat. No. 6,353,102 at column 1, line 62 to column 11, line 64, the disclosures of the aforementioned patents are incorporated herein by reference. Spiro(indoline)pyrans are also described in the text,[0085]Techniques in Chemistry, Volume III, “Photochromism”, Chapter 3, Glenn H. Brown, Editor, John Wiley and Sons, Inc., New York, 1971.
• In a further non-limiting embodiment, photochromic material (c) can be polymerizable photochromic materials, such as polymerizable naphthoxazines disclosed in U.S. Pat. No. 5,166,345 at column 3, line 36 to column 14, line 3; polymerizable spirobenzopyrans disclosed in U.S. Pat. No. 5,236,958 at column 1, line 45 to column 6, line 65; polymerizable spirobenzopyrans and spirobenzothiopyrans disclosed in U.S. Pat. No. 5,252,742 at column 1, line 45 to column 6, line 65; polymerizable fulgides disclosed in U.S. Pat. No. 5,359,085 at column 5, line 25 to column 19, line 55; polymerizable naphthacenediones disclosed in U.S. Pat. No. 5,488,119 at column 1, line 29 to column 7, line 65; polymerizable spirooxazines disclosed in U.S. Pat. No. 5,821,287 at column 3, line 5 to column 11, line 39; polymerizable polyalkoxylated naphthopyrans disclosed in U.S. Pat. No. 6,113,814 at column 2, line 23 to column 23, line 29; and the polymerizable photochromic compounds disclosed in WO97/05213 and allowed U.S. application Ser. No. 09/828,260 filed Apr. 6, 2001. The disclosures of the aforementioned patents on polymerizable photochromic materials are incorporated herein by reference.[0086]
• Other non-limiting embodiments of photochromic materials that can be used include organo-metal dithiozonates, e.g., (arylazo)-thioformic arylhydrazidates, e.g., mercury dithizonates which are described in, for example, U.S. Pat. No. 3,361,706 at column 2, line 27 to column 8, line 43; and fulgides and fulgimides, e.g., the 3-furyl and 3-thienyl fulgides and fulgimides, which are described in U.S. Pat. No. 4,931,220 at column 1, line 39 through column 22, line 41, the disclosures of which are incorporated herein by reference.[0087]
• An additional non-limiting embodiment of photochromic material (c) is a form of organic photochromic material resistant to the effects of a polymerization initiator that can also be used in the photochromic articles of the present invention. Such organic photochromic materials include photochromic compounds in admixture with a resinous material that has been formed into particles and encapsulated in metal oxides, which are described in U.S. Pat. Nos. 4,166,043 and 4,367,170 at column 1 line 36 to column 7, line 12, which disclosure is incorporated herein by reference.[0088]
• Photochromic material (b) with or without photochromic material (c) can be associated with the organic polymeric material by various methods described in the art. In alternate non-limiting embodiments, the total amount of photochromic material can be incorporated into the organic polymeric material used to form the photochromic ocular device by various methods such as by adding the photochromic materials to one or more of the materials used to form the organic polymeric material; the photochromic materials can be incorporated into the at least partially cured polymerizate by imbibition, permeation or other transfer methods as known by those skilled in the art; a polymerizable composition containing photochromic materials can be added or injected into a mold and polymerized by what, for example, is commonly referred to in the art as a cast-in-place process. When the polymerizable composition comprises highly reactive materials, e.g., materials used to form polyurethanes, a process such as reaction-injection-molding can be used.[0089]
• The term “imbibition” or “imbibe” is intended to mean and include permeation of the photochromic materials individually or with other non-photochromic materials into the polymerizate, solvent assisted transfer absorption of the photochromic materials into a polymerizate, vapor phase transfer, and other such transfer mechanisms.[0090]
• The photochromic materials described herein, e.g., photochromic materials (b) and (c), can be a variety of materials. Non-limiting examples include, of course, a single photochromic compound, a mixture of photochromic compounds, a material comprising at least one photochromic compound, such as a plastic polymeric resin or an organic monomeric or oligomeric solution, a material such as a monomer or polymer to which at least one photochromic compound is chemically bonded, a material comprising and/or having chemically bonded to it at least one photochromic compound, the outer surface of the material being encapsulated (encapsulation is a form of coating), for example with a polymeric resin or a protective coating such as a metal oxide that prevents contact of the photochromic material with external materials such as oxygen, moisture and/or chemicals that have a negative effect on the photochromic material, such materials can be formed into a particulate prior to applying the protective coating as described in U.S. Pat. Nos. 4,166,043 and 4,367,170, a photochromic polymer, e.g., a photochromic polymer comprising photochromic compounds bonded together or mixtures thereof.[0091]
• Each of photochromic materials (b) with or without the other photochromic materials (c) described herein can be used in widely varying amounts and ratios. Generally, the photochromic materials are used in such an amount or ratio that an organic polymeric material to which the photochromic materials are associated, exhibits a desired resultant color, e.g., a substantially neutral color when activated with unfiltered sunlight, e.g., as near a neutral color as possible given the colors of the activated photochromic materials, and an increased level of ultraviolet radiation absorption. In one non-limiting embodiment, the photochromic materials could be used to produce articles having a wide range of colors, e.g., pink. Further discussion of neutral colors and ways to describe colors can be found in U.S. Pat. No. 5,645,767 column 12, line 66 to column 13, line 19.[0092]
• In one non-limiting embodiment, the amount of photochromic material (b) to be incorporated into or applied to an organic polymeric material of the photochromic ocular device of the present invention can vary widely. Generally, a sufficient amount is used to produce the desired level of ultraviolet absorption. Such an amount can be described as an ultraviolet radiation absorbing amount. The particular amount used often depends upon the desired level of ultraviolet radiation absorption and the expected intensity of the ultraviolet radiation exposure. Typically, in one non-limiting embodiment, the more photochromic material (b) applied or incorporated, the greater is the amount of ultraviolet radiation absorbed up to a certain limit. There is a point after which the addition of any more material will not have a noticeable effect, although it can be added, if desired.[0093]
• In one non-limiting embodiment, the amount of photochromic material (b) to be incorporated by addition and/or imbibition into the materials used to produce the organic polymeric material can vary widely. It can range from 0.01 to 10.0 weight percent, based on the total weight of the organic polymeric material. Alternate embodiments include from 0.1 to 5 weight percent, from 0.5 to 5.0 weight percent, from 1 to 3 weight percent or from 1.5 to 2.5 weight percent. The amount of photochromic material (b) resulting in the organic polymeric material can range between any combination of these values, inclusive of the recited range, e.g., 0.011 to 9.99 weight percent.[0094]
• In one non-limiting embodiment, the amount of photochromic materials (c) to be incorporated into an organic polymeric material can vary widely. Generally, a sufficient amount is used with photochromic material (b) to produce a photochromic effect discernible to the naked eye upon activation. Such amount can be described as a photochromic amount. The particular amount used depends often upon the intensity of color desired upon irradiation thereof and upon the method used to incorporate the photochromic materials. Typically, in one non-limiting embodiment, the more photochromic incorporated, the greater is the color intensity up to a certain limit. There is a point after which the addition of any more material will not have a noticeable effect, although it can be added, if desired.[0095]
• The relative amounts of the aforesaid photochromic materials (b) or combinations thereof with photochromic materials (c) used will vary and depend in part upon the relative intensities of the color of the activated species of such materials, the ultimate color desired, the amount of ultraviolet radiation to be absorbed and the method of application to the organic polymeric material. In one non-limiting embodiment, the amount of total photochromic material which includes photochromic material (b), photochromic materials (c) or both, incorporated by imbibition or addition to the materials used to produce the organic polymeric material is the same as stated hereinabove for photochromic material (b).[0096]
• In one non-limiting embodiment, compatible (chemically and color-wise) tints, e.g., dyes, can be added or applied to the organic polymeric material used to produce the photochromic ocular device to achieve a more aesthetic result, for medical reasons, or for reasons of fashion. The particular dye selected will vary and depend on the aforesaid need and result to be achieved. In one non-limiting embodiment, the dye can be selected to complement the color resulting from the activated photochromic materials, e.g., to achieve a more neutral color or absorb a particular wavelength of incident light. In another non-limiting embodiment, the dye can be selected to provide a desired hue to the host material when the photochromic materials are in an unactivated state.[0097]
• In various non-limiting embodiments, adjuvant materials can also be incorporated into host material used to produce the photochromic article. Such adjuvants can be used, prior to, simultaneously with or subsequent to application or incorporation of the photochromic material. For example, other ultraviolet light absorbing materials discussed hereinafter can be admixed and/or reacted with photochromic materials before their addition to the composition to enhance ultraviolet radiation absorption and/or improve the light fatigue resistance of the photochromic materials. Non-limiting examples of stabilizers include hindered amine light stabilizers (HALS), asymmetric diaryloxalamide (oxanilide) compounds and singlet oxygen quenchers, e.g., a nickel ion complex with an organic ligand, polyphenolic antioxidants or mixtures of such stabilizers are contemplated. In one non-limiting embodiment, they can be used alone or in combination. Such stabilizers are known to those skilled in the art and are described in U.S. Pat. Nos. 4,720,356, 5,391,327 and 5,770,115.[0098]
• In the context of the present invention, the exact nature of the organic polymeric material is not important and a wide variety of materials can be used. Generally, materials are selected that permit the reversible tranformation of photochromic material (b) with or without photochromic material (c) between their “open” and “closed” forms. In one non-limiting embodiment, the organic polymer composition used to produce the photochromic ocular devices of the present invention comprises compositions adapted to provide thermoplastic or thermosetting organic polymeric materials that are known in the art and are described in the[0099]Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Volume 6, pages 669 to 760. Such organic polymeric materials can be transparent, translucent or opaque; but desirably are transparent.
• A wide variety of polymerizable monomers can be used to produce the organic polymeric material of the present invention. In one non-limiting embodiment, the organic polymeric material is polymerized from monomers chosen from hydroxyethyl methacrylate, N-vinyl pyrrolidone, methacrylic acid, methyl methacrylate, styrene, alpha-methylstyrene, vinyltoluene, p-chlorostyrene, o-chlorostyrene, p-bromostyrene, o-bromostyrene, divinylbenzene, divinylbiphenyl, vinyl acetate, vinyl propionate, vinyl benzoate, ethyl(meth)acrylate, isopropyl(meth)acrylate, allyl(meth)acrylate, phenyl(meth)acrylate, benzyl (meth)acrylate, p-chlorophenyl(meth)acrylate, p-chlorobenzyl (meth)acrylate, p-bromophenyl(meth)acrylate, p-bromobenzyl (meth)acrylate, naphthyl(meth)acrylate, (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-diethyl(meth)acrylamide, 2-hydroxy-3-phenoxypropyl(meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, glycerol di (meth)acrylate, 3-acryloyloxyglycerol monomethacrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, 2,2-bis(4-(meth) acryloyloxy(2′-hydroxypropyloxy)phenyl)propane, diisopropyl fumarate, diisopropyl maleate, dibenzyl fumarate, dibenzyl maleate, dibenzyl mesaconate, maleic anhydride, and itaconic anhydride. These monomers can be used alone or in mixtures thereof.[0100]
• In a further non-limiting embodiment, the monomers used to produce the organic polymeric material include monomers used to produce hydrogel polymers. A hydrogel is a crosslinked polymeric system that can absorb and retain water in an equilibrium state. Hydrogel polymers can be formed by polymerizing at least one hydrophilic monomer and at least one crosslinking agent (a crosslinking agent being defined herein as a monomer having multiple polymerizable functionalities). Representative hydrophilic monomers include: unsaturated carboxylic acids, such as methacrylic acid and acrylic acid; (meth)acrylic substituted alcohols, such as 2-hydroxyethylmethacrylate and 2-hydroxyethylacrylate; vinyl lactams, such as N-vinyl pyrrolidone; and (meth)acrylamides, such as methacrylamide and N,N-dimethylacrylamide. Non-limiting examples of crosslinking agents include polyvinyl, typically di- or tri-vinyl monomers, such as di- or tri(meth)acrylates of diethyleneglycol, triethyleneglycol, butyleneglycol and hexane-1,6-diol; and divinylbenzene. A specific example of a hydrogel polymer-forming monomer mixture is composed primarily of 2-hydroxyethylmethacrylate with a small amount of diethyleneglycol dimethacrylate as a crosslinking monomer.[0101]
• In a still further non-limiting embodiment, the polymerizable monomer mixture can optionally include a silicone-containing monomer in order to form a silicone hydrogel polymer. A silicone-containing monomer is one that contains at least one [—Si—O—] group in a monomer, macromer or prepolymer. Non-limiting examples of silicone-containing monomers include: monomers including a single activated unsaturated radical, such as methacryloxypropyl tris(trimethylsiloxy)silane, pentamethyldisiloxanyl methylmethacrylate, tris(trimethylsiloxy)-methacryloxypropylsilane, methyldi(trimethylsiloxy)-methacryloxymethylsilane, 3-[tris(trimethylsiloxy)silyl]propyl vinylcarbamate, and 3-[tris(trimethylsiloxy)silyl]propylvinyl carbonate; and multifunctional ethylenically “end-capped” siloxane-containing monomers, e.g., difunctional monomers having two activated unsaturated radicals. A specific example of a silicone hydrogel polymer-forming monomer mixture is balafilcon, based on N-vinyl pyrrolidone and the aforementioned vinyl carbonate and carbamate monomers, disclosed in U.S. Pat. No. 5,260,000. Non-limiting examples of silicone-containing monomers are disclosed in U.S. Pat. No. 6,020,445 at column 4, line 48 to column 8, line 45, which disclosure is incorporated herein by reference. Many other lens-forming monomers and specific mixtures thereof are well known in the art, e.g., monomers disclosed in U.S. Pat. No. 5,637,726 at column 3, line 40 to column 4, line 8.[0102]
• In another non-limiting embodiment, ultraviolet radiation absorbing materials can be used to enhance the reduction in ultraviolet radiation by photochromic material (b). Such materials include ultraviolet absorbing monomers. Non-limiting examples of such materials include: benzotriazole (meth)acrylate esters, e.g., 2-[2′-hydroxy-5′-acryloyloxyalkylphenyl]2H-benzotriazoles, 2-[2′-hydroxy-5′-acryloyloxy-alkoxyphenyl]2H-benzotriazoles, and 2-(2′-hydroxyphenyl)-5(6)-(acryloylalkoxy)benzotriazoles.[0103]
• Non-limiting examples of benzotriazole UV-absorbing (meth)acrylate esters that can be used in the invention include the following materials: 2-(2′-hydroxy-5′-methacryloxyethyl-phenyl)-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxyethyl-phenyl)-5-chloro-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxy-propylphenyl)-5-chloro-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxypropyl-3′-tert-butylphenyl)-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxypropyl-3′-tert-butylphenyl)-5-chloro-2H-benzotriazole; 2-[2′-hydroxy-5′-(2-methacryloyloxyethoxy)-3′-tert-butylphenyl]-5-methoxy-2H-benzotriazole; 2-[2′-hydroxy-5′-(gamma-methacryloyloxypropoxy)-3′-tert-butylphenyl]-5-methoxy-2H-benzotriazole; 2-(3′-t-butyl-2′-hydroxy-5′-methoxyphenyl)-5-(3′-methacryloyloxypropoxy)benzotriazole or mixtures thereof.[0104]
• In another non-limiting embodiment of the present invention, photochromic materials (b) can be used in conjunction with a reduced level of the aforementioned non-photochromic UV absorbing materials to produce a photochromic ocular device that meets recommended guidelines for the transmission of ultraviolet radiation through such devices.[0105]
• In one non-limiting embodiment, a general method for incorporating photochromic materials (b) with or without photochromic materials (c) into ocular devices, e.g., hydrophilic contact lenses, is disclosed in U.S. Pat. No. 6,224,945 B1 at column 5 lines 1 to 47, which disclosure is incorporated herein by reference. In that method, an impregnating solution is used which has a concentration of photochromic material generally from 0.0001 to 1 percent by weight in one embodiment. In an alternate embodiement, the impregnating solution can have a concentration of from 0.05 to 0.25 percent by weight.[0106]
• The impregnating of the contact lens material is generally carried out by immersion, at room temperature, of the polymeric material in the photochromic solution with stirring. The duration of immersion varies according to the nature of the polymeric material and of the photochromic solution and, in one non-limiting embodiment, it is about 5 minutes.[0107]
• After impregnating, the polymeric material is treated with an aqueous solution, e.g., physiological saline, in order to replace the impregnated solvent with the aqueous solution.[0108]
• In an alternative non-limiting embodiment, photochromic material (b) with or without photochromic material (c) can be incorporated into ocular devices, e.g., hydrophilic contact lenses, using mold casting techniques. The mold casting technique comprises the direct molding of a monomer mixture wherein said mixture including the photochromic material is dissolved in a non-aqueous, water-displaceable solvent. The resulting mixture is placed in a mold having the shape of the final desired photochromic ocular device, and subjected to conditions whereby the monomer(s) polymerize, to thereby produce a polymerizate in the shape of the final desired photochromic ocular device.[0109]
• Polymerization is typically carried out in a substantially non-aqueous medium because water can inhibit the polymerization reaction. After the polymerization is complete, the solvent is displaced with water to produce a hydrated lens whose final size and shape are quite similar to the size and shape of the original casting mold. A direct molding process of hydrogel contact lenses is disclosed in U.S. Pat. No. 4,495,313 at column 2, line 43 to column 6, line 56, and in U.S. Pat. No. 4,680,336 at column 4 line 45 to column 12 line 5, which disclosures are incorporated herein by reference.[0110]
• The present invention is more particularly described in the following Example and Comparative Example, which are intended as illustrative only, since numerous modifications and variations therein will be apparent to those skilled in the art.[0111]
EXAMPLE
• The Ultraviolet Photochromic Performance Test was conducted on the lens by measuring the activated and unactivated spectra over a wavelength range of from 300 to 700 nm and determining the ratio of increased ultraviolet radiation absorbance to increased visible radiation absorbance as described hereinbelow.[0112]
• A hydrophilic contact lens composed of methylmethacrylate and N-vinylpyrrolidone in a 28:72 weight ratio, which composition is equivalent to that of the Rythmic® contact lens available from Essilor International, except that it did not contain a UV absorber, was used. The lens, in the hydrated state, was immersed in a vessel containing 2 milliliters (mL) of dimethyl sulfoxide (DMSO) solution having 0.05 weight percent of 3-(4-methoxyphenyl)-3-phenyl-6,11-dimethoxy-13-methyl-13-(2-(2-hydroxyethyl)ethoxy)-3H, 13H-indeno[2,′3,′3,4]-naphtho-[1,2-b]pyran. The aforementioned weight percent is based on the total weight of the solution. The immersed lens was stirred for a period of 5 minutes at room temperature. Afterwards, the lens was rinsed with physiological saline and immersed in physiological saline until the initial diameter was recovered (approximately ten minutes). The resulting lens was steam sterilized at 121° C. for 20 minutes.[0113]
• After cooling to room temperature, the hydrated lens was placed in a quartz Special Cell measuring 30 mm by 22 mm by 3 mm, made by Starna Cells, Inc., containing physiological saline. The Special Cell was then placed in a carrier suitable for use in a Cary Ultraviolet/Visible spectrophotometer Model # 4000. An Ultraviolet-Visible absorption spectrum was collected before exposure to UV and after the lens was exposed to enough UV radiation to lower the visible light transmittance to of 30 percent through the lens. This was accomplished by exposing the lens in the holder to radiation from a Spectroline Long-Wavelength (365 nm) lamp for 15 to 20 seconds.[0114]
• The resulting spectra were analyzed and the ratio of increased ultraviolet absorbance and increased visible absorbance were determined by measuring the greatest difference in absorbance between the unactivated and activated spectra lines in the ultraviolet range of from 300 to 400 nanometers and dividing that number by the greatest difference between the unactivated and activated spectra lines in the visible range of from 400 to 700 nanometers. The spectrum for the Example of the present invention is shown in FIG. 1. The greatest difference in absorbance in the ultraviolet spectrum is 28 millimeters (mm) at 385 nm and the greatest difference in the visible spectrum is 30 mm at 575 nm. The resulting ratio is 0.93:1.0.[0115]
Comparative Example
• The procedure of the Example was followed except that Photochromic compound (I) from U.S. Pat. No. 6,224,945 B1, which is reported to be 3,3-di(4-methoxyphenyl)-6,11-dimethyl-13-methyl-13-hydroxy-indeno[2,′3,′3,4]naphtho[1,2-b]pyran, was used. The spectrum of the Comparative Example is shown in FIG. 2. The greatest difference in absorbance in the ultraviolet spectrum is 13 millimeters (mm) at 315 nm and the greatest difference in the visible spectrum is 31 mm at 555 nm. The resulting ratio is 0.42:1.0.[0116]
• From the spectra presented in FIG. 1, it is apparent that upon activation, the lens develops absorbance not only in the visible portion of the spectrum (providing protection from glare), but also in the ultraviolet portion of the spectrum.[0117]
• An estimate of the increase in absorbance can be made directly from the graph in absorbance units instead of by measuring the distance between the lines as done hereinabove. The increase in absorbance at 385 nm (1.0 -0.5=0.5) is nearly equivalent to the absorbance at 575nm (absorbance=0.5). Therefore the ratio in the Ultraviolet Photochromic Performance Test is 1.0:1.0.[0118]
• From the spectra presented in FIG. 2, the increase in absorbance at 315 nm is 0.2 and the increase in absorbance at 555 nm is 0.4. The resulting ratio in the Ultraviolet Photochromic Performance Test is 0.5:1.0.[0119]
• While the present invention has been described with respect to particular embodiments of apparatus, methods and materials, it will be appreciated that various modifications and adaptations can be made based on the present disclosure and are intended to be within the scope of the accompanying claims.[0120]

Claims (23)

I claim:

1. A photochromic ocular device comprising:

(a) an organic polymeric material; and

(b) at least one photochromic material adapted to change from a less radiation absorbing unactivated form to a more radiation absorbing activated form upon exposure to actinic radiation;

said photochromic ocular device being adapted upon exposure to actinic radiation to exhibit a ratio of increased ultraviolet radiation absorbance to increased visible radiation absorbance of greater than 0.5:1.0 as measured in the Ultraviolet Photochromic Performance Test.

2. The photochromic ocular device ofclaim 1 wherein the photochromic material (b) is chosen from 3H-naphtho[2,1-b]pyrans, 2H-naphtho[1,2-b]pyrans, indeno[2,′3,′3,4]naphtho[1,2-b]pyrans, or mixtures thereof.

3. The photochromic ocular device ofclaim 2 wherein the photochromic material (b) is an indeno[2,′3,′3,4]naphtho[1,2-b]pyrans.

4. The photochromic ocular device ofclaim 1 wherein photochromic material (b) is represented by a graphic formula chosen from I, II, III or mixtures thereof:

wherein,

(a) R₁is the group R which is represented by one of the following formulae (IVA) to (IVF):

—A (formula IVA);

—D—A (formula TVB);

—D—E—U (formula IVC);

—D—U (formula IVD);

—E—U (formula IVE); or

—U (formula IVF);

wherein —A is represented by the following formula:

—[(OC₂H₄)_x(OC₃H₆)_y(OC₄H₈)_z]—J

wherein —J is chosen from: hydroxy, (meth)acryloxy, 2-(methacryloxy)ethylcarbamyl, epoxy, C₁-C₆alkyl, —OCH₂COOH; —OCH(CH₃)COOH; —OC(O) (CH₂)_wCOOH; —OC₆H₄SO₃H; —OC₅H₁₀SO₃H; —OC₄H₈SO₃H; —OC₃H₆SO₃H; —OC₂H₄SO₃H; or —OSO₃H; w is an integer from 1 to 18; x, y and z are each a number between 0 and 50, and the sum of x, y and z is between 1 and 50; —D—is —C(O)— or —CH₂—; —E— is represented by the following formula:

—[(OC₂H₄)_x(OC₃H₆)_y(OC₄H₈)_z]—

wherein x, y and z are the same as defined for —A; —U is a residue of an organic polyol having at least one hydroxyl group or a derivative of said residue wherein at least one hydroxyl group has been reacted to form the group J provided that —U is not the same as —A when —J is hydroxy; or R₁is hydrogen, C₁-C₃alkyl or the group, —C(O)W, W being —OR₇, —N(R₈)R₉, piperidino or morpholino, wherein R₇is allyl, C₁-C₆alkyl, phenyl, mono(C₁-C₆)alkyl substituted phenyl, mono(C₁-C₆)alkoxy substituted phenyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl or C₁-C₆haloalkyl; R₈and R₉are each independently chosen from C₁-C₆alkyl, C₅-C₇cycloalkyl, phenyl, mono-substituted phenyl or di-substituted phenyl, said phenyl substituents being C₁-C₆alkyl or C₁-C₆alkoxy, and said halo substituent being chloro or fluoro;

(b) R₁′ is the group R, C₁-C₃alkyl or the group, —C(O)W, W being —OR₇, —N(R₈)R₉, piperidino or morpholino, wherein R₇is allyl, C₁-C₆alkyl, phenyl, mono(C₁-C₆)alkyl substituted phenyl, mono(C₁-C₆)alkoxy substituted phenyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl or C₁-C₆haloalkyl; R₈and R₉are each independently chosen from C₁-C₆alkyl, C₅-C₇cycloalkyl, phenyl, mono-substituted phenyl or di-substituted phenyl, said phenyl substituents being C₁-C₆alkyl or C₁-C₆alkoxy, and said halo substituent being chloro or fluoro;

(c) R₂is chosen from the group R, mono-R-substituted phenyl, hydrogen, C₁-C₆alkyl, C₃-C₇cycloalkyl, phenyl, mono-substituted phenyl, di-substituted phenyl, the group —OR₁₀or —OC(O)R₁₀, wherein R₁₀is C₁-C₆alkyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl, C₃-C₇cycloalkyl or mono(C₁-C₄)alkyl substituted C₃-C₇cycloalkyl, and said phenyl substituent being C₁-C₆alkyl or C₁-C₆alkoxy;

(d) each R₃and each R₄are independently chosen from the group R, hydrogen, C₁-C₆alkyl, C₃-C₇cycloalkyl, phenyl, mono-substituted phenyl, di-substituted phenyl, the group —OR₁₀or —OC(O)R₁₀, wherein R₁₀is C₁-C₆alkyl, phenyl(C₁-C₃)-alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl, C₃-C₇cycloalkyl or mono(C₁-C₄)alkyl substituted C₃-C₇cycloalkyl, and said phenyl substituent being C₁-C₆alkyl or C₁-C₆alkoxy; or each R₃and each R₄are independently a nitrogen-containing group chosen from:

(i) —N(R₁₁)R₁₂wherein R₁₁and R₁₂are each independently chosen from hydrogen, C₁-C₈alkyl, phenyl, naphthyl, furanyl, benzofuran-2-yl, benzofuran-3-yl, thienyl, benzothien-2-yl, benzothien-3-yl, dibenzofuranyl, dibenzothienyl, benzopyridyl and fluorenyl, C₁-C₈alkylaryl, C₃-C₂₀cycloalkyl, C₄-C₂₀bicycloalkyl, C₅-C₂₀tricycloalkyl or C₁-C₂₀alkoxyalkyl, wherein said aryl group is phenyl or naphthyl or R₁₁and R₁₂come together with the nitrogen atom to form a C₃-C₂₀hetero-bicycloalkyl ring or a C₄-C₂₀hetero-tricycloalkyl ring;

(ii) a nitrogen containing ring represented by the following graphic formula VA:

 wherein each Y is independently chosen for each occurrence from —CH₂—, —CH(R₁₃)—, —C(R₁₃)(R₁₃)—, —CH(aryl)—, —C(aryl)₂—, or —C(R₁₃)(aryl)—, and X is chosen from —Y—, —O—, —S—, —S(O)—, —S(O₂)—, —NH—, —N(R₁₃)— or —N(aryl)—, wherein R₁₃is C₁-C₆alkyl, said aryl is phenyl or naphthyl, m is the integer 1, 2 or 3, and p is the integer 0, 1, 2, or 3 and when p is 0, X is Y;

(iii) a group represented by one of the following graphic formulae VB or VC:

 wherein R₁₅, R₁₆and R₁₇are each independently chosen for each occurrence in each formula from hydrogen, C₁-C₆alkyl, phenyl or naphthyl, or the groups R₁₅and R₁₆together form a ring of 5 to 8 carbon atoms and each R₁₄is independently chosen for each occurrence in each formula from C₁-C₆alkyl, C₁-C₆alkoxy, fluoro or chloro and p is the same as defined hereinbefore;

(iv) unsubstituted, mono- or di-substituted C₄-C₁₈spirobicyclic amine; or

(v) unsubstituted, mono- or di-substituted C₄-C₁₈spirotricyclic amine; said substituents for (d)(iv) and (v) are independently chosen for each occurrence from aryl, C₁-C₆alkyl, C₁-C₆alkoxy or phenyl(C₁-C₆)alkyl and n is chosen from the integers 0, 1 or 2;

(e) R₅and R₆together form an oxo group, a spiro-carbocyclic ring containing 3 to 6 carbon atoms or a spiro-heterocyclic group containing 1 or 2 oxygen atoms and 3 to 6 carbon atoms including the spirocarbon atom, said spiro-carbocyclic and spiro-heterocyclic groups being annellated with 0, 1 or 2 benzene rings; or R₅and R₆are each independently the group R, hydrogen, hydroxy, C₁-C₆alkyl, C₃-C₇cycloalkyl, allyl, phenyl, mono-substituted phenyl, benzyl, mono-substituted benzyl, chloro, fluoro, the group, —C(O)X′, wherein X′is hydroxy, C₁-C₆alkyl, C₁-C₆alkoxy, phenyl, mono-substituted phenyl, amino, mono(C₁-C₆)alkylamino, or di(C₁-C₆)alkylamino; or R₅and R₆are each independently the group, —OR₁₈, wherein R₁₈is C₁-C₆alkyl, phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₆)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₆alkoxy(C₂-C₄)alkyl, C₃-C₇cycloalkyl, mono(C₁-C₄)alkyl substituted C₃-C₇cycloalkyl, C₁-C₆chloroalkyl, C₁-C₆fluoroalkyl, allyl, the group, —CH(R₁g)Y′, wherein R₁₉is hydrogen or C₁-C₃alkyl and Y′ is CN, CF₃, or COOR₂₀and R₂₀is hydrogen or C₁-C₃alkyl; or R₁₈is the group, —C(O)Z, wherein Z is hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy, the unsubstituted, mono- or di-substituted aryl groups phenyl or naphthyl, phenoxy, mono- or di-(C₁-C₆)alkyl substituted phenoxy, mono- or di-(C₁-C₆)alkoxy substituted phenoxy, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, phenylamino, mono- or di-(C₁-C₆)alkyl substituted phenylamino, or mono- or di-(C₁-C₆)alkoxy substituted phenylamino, each of said phenyl, benzyl and aryl group substituents being C₁-C₆alkyl or C₁-C₆alkoxy;

(f) B and B′ are each independently chosen from:

(i) the unsubstituted, mono-, di-or tri- substituted aryl groups, phenyl or naphthyl;

(ii) 9-julolidinyl or the unsubstituted, mono- or di-substituted heteroaromatic groups pyridyl, furanyl, benzofuran-2-yl, benzofuran-3-yl, thienyl, benzothien-2-yl, benzothien-3-yl, dibenzofuranyl, dibenzothienyl, carbazolyl or fluorenyl, each of said aryl and heteroaromatic substituents in (f)(i) and (ii) being chosen from the group R, hydroxy, aryl, mono(C₁-C₆)alkoxyaryl, di(C₁-C₆)alkoxyaryl, mono(C₁-C₆)alkylaryl, di(C₁-C₆)alkylaryl, chloroaryl, fluoroaryl, C₃-C₇cycloalkylaryl, C₃-C₇cycloalkyl, C₃-C₇cycloalkyloxy, C₃-C₇cycloalkyloxy(C₁-C₆)alkyl, C₃-C₇cycloalkyloxy(C₁-C₆)alkoxy, aryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkoxy, aryloxy, aryloxy(C₁-C₆)alkyl, aryloxy(C₁-C₆)alkoxy, mono- or di-(C₁-C₆)alkylaryl(C₁-C₆)alkyl, mono- or di-(C₁-C₆)alkoxyaryl(C₁-C₆)alkyl, mono- or di-(C₁-C₆)alkylaryl(C₁-C₆)alkoxy, mono- or di-(C₁-C₆)alkoxyaryl(C₁-C₆)alkoxy, amino, mono(C₁-C₆)alkylamino, di(C₁-C₆)alkylamino, diarylamino, N-(C₁-C₆)alkylpiperazino, N-arylpiperazino, aziridino, indolino, piperidino, arylpiperidino, morpholino, thiomorpholino, tetrahydroquinolino, tetrahydroisoquinolino, pyrryl, C₁-C₆alkyl, C₁-C₆chloroalkyl, C₁-C₆fluoroalkyl, C₁-C₆alkoxy, mono(C₁-C₆)alkoxy(C₁-C₄)alkyl, acryloxy, methacryloxy, bromo, chloro or fluoro, said aryl being phenyl or naphthyl;

(iii) the unsubstituted or mono-substituted groups, pyrazolyl, imidazolyl, pyridyl, pyrazolinyl, imidazolinyl, pyrrolinyl, phenothiazinyl, phenoxazinyl, phenazinyl or acridinyl, each of said substituents being chosen from C₁-C₆alkyl, C₁-C₄alkoxy, phenyl, fluoro, chloro or bromo;

(iv) monosubstituted phenyl, having at the para position a substituent that is —(CH₂)_t— or —O—(CH₂)_t—, wherein t is the integer 1, 2, 3, 4, 5 or 6, said substituent being connected to an aryl group on another photochromic material;

(v) the group represented by one of the following graphic formulae VIA or VIB:

 wherein L is carbon or oxygen and M is oxygen or substituted nitrogen, provided that when M is substituted nitrogen, L is carbon, said nitrogen substituents being chosen from hydrogen, C₁-C₆alkyl and C₂-C₆acyl; each R₂₁is C₁-C₆alkyl, C₁-C₆alkoxy, hydroxy, chloro or fluoro; R₂₂and R₂₃are each hydrogen or C₁-C₆alkyl; and q is the integer 0, 1 or 2;

(vi) C₁-C₆alkyl, C₁-C₆chloroalkyl, -C₁-C₆fluoroalkyl, C₁-C₆alkoxy(C₁-C₄)alkyl, C₃-C₆cycloalkyl, mono(C₁-C₆)alkoxy(C₃-C₆)cycloalkyl, mono(C₁-C₆)alkyl(C₃-C₆)-cycloalkyl, chloro(C₃-C₆)cycloalkyl, fluoro(C₃-C₆)cycloalkyl or C₄-C₁₂bicycloalkyl; and

(vii) the group represented by the following graphic formula VIC:

wherein P is hydrogen or C₁-C₄alkyl and Q is chosen from an unsubstituted, mono- or di-substituted group, said group being chosen from naphthyl, phenyl, furanyl or thienyl, each of said group substituents being C₁-C₄alkyl, C₁-C₄alkoxy, fluoro or chloro; or

(g) B and B′ taken together form fluoren-9-ylidene, mono-, or di-substituted fluoren-9-ylidene or a member chosen from saturated C₃-C₁₂spiro-monocyclic hydrocarbon rings, saturated C₇-C₁₂spiro-bicyclic hydrocarbon rings, or saturated C₇-C₁₂spiro-tricyclic hydrocarbon rings, each of said fluoren-9-ylidene substituents being chosen from C₁-C₄alkyl, C₁-C₄alkoxy, fluoro or chloro.

5. The photochromic ocular device ofclaim 4 wherein photochromic material (b) is represented by graphic formula I, III or mixtures thereof, wherein:

(a) R₁′ is the group R represented by formulae: (IVA); (IVB); (IVE); or (IVF); or R₁′ is the group, —C(O)W, W being —OR₇or —N(R₈)R₉, wherein R₇is C₁-C₄alkyl, phenyl, mono(C₂-C₄)alkyl substituted phenyl, mono(C₁-C₄)alkoxy substituted phenyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkyl substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkoxy substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkoxy(C₂-C₃)alkyl or C₁-C₄haloalkyl; R₈and R₉are each chosen independently from C₁-C₄alkyl, C₅-C₇cycloalkyl, phenyl, mono-substituted phenyl or di-substituted phenyl, said phenyl substituents being C₁-C₄alkyl or C₁-C₄alkoxy, said halo substituents being chloro or fluoro;

(b) R₂is chosen from the group R, mono-R-substituted phenyl, hydrogen, C₁-C₃alkyl, C₃-C₅cycloalkyl, phenyl, mono-substituted phenyl, di-substituted phenyl or the group —OR₁₀, wherein R₁₀is C₁-C₄alkyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkyl substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkoxy substituted phenyl(C₁-C₂)alkyl, C₁-C₄alkoxy(C₂-C₄)alkyl, C₅-C₇cycloalkyl or mono(C₁-C₃)alkyl substituted C₅-C₇cycloalkyl; said phenyl substituents being C₁-C₃alkyl or C₁-C₃alkoxy;

(c) each R₃is independently chosen from the group R or the group —OR₁₀, wherein R₁₀is C₁-C₄alkyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkyl substituted phenyl(C₁-C₂)alkyl, mono(C₁-C₄)alkoxy substituted phenyl(C₁-C₂)alkyl, C₁-C₄alkoxy(C₂-C₄)alkyl, C₅-C₇cycloalkyl or mono(C₁-C₃)alkyl substituted C₅-C₇cycloalkyl and said phenyl substituents being C₁-C₃alkyl or C₁-C₃alkoxy; or each R₃is independently a nitrogen-containing group chosen from:

(i) —N(R₁₁)R₁₂, R₁₁and R₁₂each being independently chosen from C₁-C₆alkyl or phenyl;

(ii) a nitrogen containing ring represented by the graphic formula VA wherein each Y being —CH₂— and X being independently chosen from —Y—, —O—, —S—, —N(R₁₃)— and —N(phenyl)—, R₁₃being C₁-C₆alkyl, m being chosen from the integer 1, 2 or 3, and p being chosen from the integer 0, 1, 2 or 3;

(iii) a group represented by one of graphic formulae VB or VC wherein R₁₅, R₁₆and R₁₇each being independently chosen from hydrogen or C₁-C₅alkyl, R₁₄being independently chosen from hydrogen, C₁-C₄alkyl, C₁-₄alkoxy, fluoro or chloro;

(iv) unsubstituted or mono-substituted C₅-C₁₈spirobicyclic amine; or

(v) unsubstituted or mono-substituted C₅-C₁₈spirotricyclic amine; said substituents for (c)(iv) and (v) are independently chosen for each occurrence from phenyl, C₁-C₆alkyl or C₁-C₆alkoxy and n being chosen from the integer 1 or 2;

(d) R₅and R₆are each independently chosen from the group R, hydrogen, hydroxy, C₁-C₄alkyl, C₃-C₆cycloalkyl, chloro, fluoro and the group, —OR₁₈, wherein R₁₈is C₁-C₃alkyl, phenyl(C₁-C₂)alkyl, mono(C₁-C₃)alkyl substituted phenyl(C₁-C₃)alkyl, mono(C₁-C₃)alkoxy substituted phenyl(C₁-C₃)alkyl, C₁-C₃alkoxy(C₂-C₄)alkyl, C₁-C₃chloroalkyl, C₁-C₃fluoroalkyl, the group, —CH(R₁₉)Y′, wherein R₁₉is hydrogen or C₁-C₂alkyl and Y′ is CN or COOR₂₀, and R₂₀is hydrogen or C₁-C₂alkyl, or R₁₈is the group, —C(O)Z, wherein Z is hydrogen, C₁-C₃alkyl, C₁-C₃alkoxy, phenyl, naphthyl, mono-substituted aryl groups, phenyl or naphthyl, phenoxy, mono- or di-(C₁-C₃)alkyl substituted phenoxy, mono- or di-(C₁-C₃)alkoxy substituted phenoxy, mono(C₁-C₃)alkylamino, phenylamino, mono- or di-(C₁-C₃)alkyl substituted phenylamino, or mono- or di-(C₁-C₃)alkoxy substituted phenylamino, and said aryl substituents being C₁-C₃alkyl or C₁-C₃alkoxy;

(e) B and B′ are each independently chosen from:

(i) phenyl, mono-substituted or di-substituted phenyl, each of said phenyl substituents being independently chosen from the group R, hydroxy, aryl, arlyoxy, aryl(C₁-C₃)alkyl, amino, mono(C₁-C₃)alkylamino, di(C₁-C₃)alkylamino, N-(C₁-C₃)alkylpiperazino, indolino, piperidino, morpholino, pyrryl, C₁-C₃alkyl, C₁-C₃chloroalkyl, C₁-C₃fluoroalkyl, C₁-C₃alkoxy, mono(C₁-C₃)alkoxy(C₁-C₃)alkyl, chloro or fluoro;

(ii) the groups represented by one of graphic formulae VIA or VIB: wherein L is carbon and M is oxygen, R₂₁is C₁-C₃alkyl or C₁-C₃alkoxy; R₂₂and R₂₃are each hydrogen or C₁-C₄alkyl; and q is 0 or 1;

(iii) C₁-C₄alkyl; or

(iv) the group represented by graphic formula VIC wherein P is hydrogen or methyl and Q is phenyl or mono- substituted phenyl, said phenyl substituents being C₁-C₃alkyl, C₁-C₃alkoxy or fluoro; or

(f) B and B′ taken together form fluoren-9-ylidene, mono-substituted fluoren-9-ylidene or a member chosen from saturated C₃-C₈spiro-monocyclic hydrocarbon rings, saturated C₇-C₁₀spiro-bicyclic hydrocarbon rings, or saturated C₇-C₁₀spiro-tricyclic hydrocarbon rings, said fluoren-9-ylidene substituent being chosen from C₁-C₃alkyl, C₁-C₃alkoxy, fluoro or chloro.

6. The photochromic ocular device ofclaim 5 wherein photochromic material (b) is represented by graphic formula III wherein:

(a) each R₃is the group R represented by formula (IVE) or (IVF), or the group, OR₁₀, wherein R₁₀is C₁-C₃alkyl; or each R₃is chosen from:

(i) —N(R₁₁)R₁₂, R₁₁and R₁₂each being C₁-C₃alkyl;

(ii) a nitrogen containing ring represented by graphic formula VA wherein each Y for each occurrence being —CH₂— and X being independently chosen from —Y—, —O—, and —N(R₁₃)—, R₁₃being C₁-C₄alkyl, m being chosen from the integer 1 or 2, and p being chosen from the integer 0, 1 or 2; or

(iii) a group represented by graphic formulae VC or VB wherein R₁₅, R₁₆, and R₁₇each being hydrogen and n is 1 or 2;

(b) R₅and R₆are each the group R, hydrogen, hydroxy, C₁-C₄alkyl, or the group, —OR₁₈, wherein R₁₈is C₁-C₃alkyl;

(c) B and B′ are each independently chosen from:

(i) phenyl, mono- or di-substituted phenyl, each of said phenyl substituents being chosen from the group R, hydroxy, C₁-C₃alkyl, C₁-C₃alkoxy, phenyl, piperidino, morpholino, fluoro or chloro; or

(d) B and B′ taken together form fluoren-9-ylidene, adamantylidene, bornylidene, norbornylidene, or bicyclo[3.3.1]nonan-9-ylidene.

7. The photochromic ocular device ofclaim 5 wherein photochromic material (b) is chosen from:

(a) 3-(4-methoxyphenyl)-3-phenyl-6,11-dimethoxy-13-methyl-13-(2-{2-[N-(2-methacryloxyethyl)carbamoyloxy]ethoxy) ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;

(b) 3-(4-methoxyphenyl)-3-phenyl-6,11-dimethoxy-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;

(c) 3,3-diphenyl-6,7-dimethoxy-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho [1,2-b]pyran;

(d) 3-(4-methoxyphenyl)-3-(2,4-dimethoxyphenyl-6,11-dimethoxy-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;

(e) 3-(4-methoxyphenyl)-3-phenyl-6-methoxy-7-morpholino-13-methyl-13-(2-(2-(2-methacryloxyethyl)ethoxy)ethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;

(f) 3,3-diphenyl-6,7,10,11-tetramethoxy-13-ethyl-13-(2-{2-[N-(2-methacryloxyethyl)carbamoyloxy]ethoxylethoxy)-3H,13H-indeno[2,′3,′3,4]naphtho[1,2-b]pyran;

(g) 2,2-diphenyl-5-(2-(2-(2-methacryloxyethyl)ethoxy) ethoxy)carbonyl-9-methoxy-2H-naphtho[1,2-b]pyran;

(h) 2,2-di(4-fluorophenyl)-5-(2-(2-(2-methacryloxy-ethyl)ethoxy)ethoxy)carbonyl-6-phenyl-9-methoxy-2H-naphtho[1,2-b]pyran;

(i) 2,2-diphenyl-5-(2-(2-(2-methacryloxyethyl)ethoxy) ethoxy)carbonyl-8,9-dimethoxy-2H-naphtho[1,2-b]pyran; or

(j) mixtures thereof.

8. The photochromic ocular device ofclaim 1 wherein photochromic material (b) is chosen from:

(a) a single photochromic compound;

(b) a mixture of photochromic compounds;

(c) a material comprising at least one photochromic compound;

(d) a material to which at least one photochromic compound is chemically bonded;

(e) material (c) or (d) comprising a coating to substantially prevent contact of the at least one photochromic compound with external materials;

(f) a photochromic polymer; or

(g) mixtures thereof.

9. The photochromic ocular device ofclaim 1 further comprising at least one other photochromic material (c) that is different from photochromic material (b).

10. The photochromic ocular device ofclaim 9 wherein photochromic compound (c) is an organic photochromic compound.

11. The photochromic ocular device ofclaim 10 wherein photochromic compound (c) is an organic photochromic compound and is chosen from chromenes; spiropyrans; oxazines; mercury dithizonates, fulgides, fulgimides or mixtures thereof.

12. The photochromic ocular device ofclaim 11 wherein photochromic compound (c) is an organic photochromic compound and is chosen from chromenes comprising naphthopyrans, benzopyrans, indenonaphthopyrans, phenanthropyrans or mixtures thereof.

13. The photochromic ocular device ofclaim 12 wherein photochromic compound (c) is an organic photochromic compound and is chosen from naphthopyrans, indenonaphthopyrans, or a mixture thereof.

14. The photochromic ocular device ofclaim 9 wherein photochromic material (c) is chosen from:

(a) a single photochromic compound;

(b) a mixture of photochromic compounds;

(c) a material comprising at least one photochromic compound;

(d) a material to which at least one photochromic compound is chemically bonded;

(e) material (c) or (d) comprising a coating to substantially prevent contact of the at least one photochromic compound with external materials;

(f) a photochromic polymer; or

(g) mixtures thereof.

15. The photochromic ocular device ofclaim 1 wherein the organic polymeric material is polymerized from monomers chosen from hydroxyethyl methacrylate, N-vinyl pyrrolidone, methacrylic acid, methyl methacrylate, styrene, alpha-methylstyrene, vinyltoluene, p-chlorostyrene, o-chlorostyrene, p-bromostyrene, o-bromostyrene, divinylbenzene, divinylbiphenyl, vinyl acetate, vinyl propionate, vinyl benzoate, ethyl(meth)acrylate, isopropyl(meth)acrylate, allyl(meth)acrylate, phenyl(meth)acrylate, benzyl (meth)acrylate, p-chlorophenyl(meth)acrylate, p-chlorobenzyl (meth)acrylate, p-bromophenyl(meth)acrylate, p-bromobenzyl (meth)acrylate, naphthyl(meth)acrylate, (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-diethyl(meth)acrylamide, 2-hydroxy-3-phenoxypropyl(meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, glycerol di(meth)acrylate, 3-acryloyloxyglycerol monomethacrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, 2,2-bis(4-(meth) acryloyloxy(2′-hydroxypropyloxy)phenyl)propane, diisopropyl fumarate, diisopropyl maleate, dibenzyl fumarate, dibenzyl maleate, dibenzyl mesaconate, maleic anhydride, itaconic anhydride or mixtures thereof.

16. The photochromic ocular device ofclaim 1 wherein the ratio of increased ultraviolet radiation absorbance to increased visible radiation absorbance as measured in the Ultraviolet Photochromic Performance Test is at least 1.0:1.0.

17. The photochromic ocular device ofclaim 1 wherein the organic polymeric material is a hydrogel polymer comprising a polymerizate of at least one hydrophilic monomer and at least one crosslinking agent.

18. The photochromic ocular device ofclaim 17 wherein the at least one hydrophilic monomer is chosen from: unsaturated carboxylic acids; (meth)acrylic substituted alcohols; vinyl lactams; (meth)acrylamides; or mixtures thereof.

19. The photochromic ocular device ofclaim 17 wherein the at least one crosslinking agent is chosen from divinylbenzene; di-or tri(meth)acrylates of diethyleneglycol, triethyleneglycol, butyleneglycol or hexane-1,6-diol; or mixtures thereof.

20. The photochromic ocular device ofclaim 17 wherein the organic polymeric material is a hydrogel polymer further comprising at least one silicone-containing monomer comprising at least one unsaturated group.

21. The photochromic ocular device ofclaim 20 wherein the at least one silicone-containing monomer comprising at least one unsaturated group is chosen from methacryloxypropyl tris(trimethylsiloxy)silane, pentamethyldisiloxanyl methylmethacrylate, tris(trimethylsiloxy)methacryloxy propylsilane, methyldi(trimethylsiloxy)methacryloxymethyl silane, 3-[tris(trimethylsiloxy)silyl]propylvinylcarbamate, or 3-[tris(trimethylsiloxy)silyl]propylvinylcarbonate.

22. The photochromic ocular device ofclaim 1 further comprising at least one ultraviolet absorbing material.

23. The photochromic ocular device ofclaim 22 wherein the at least one ultraviolet absorbing material is a monomer chosen from: 2-(21-hydroxy-5′-methacryloxyethyl-phenyl)-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxyethyl-phenyl)-5-chloro-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxy-propylphenyl)-5-chloro-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxypropyl-3′-tert-butylphenyl)-2H-benzotriazole; 2-(2′-hydroxy-5′-methacryloxypropyl-3′-tert-butylphenyl)-5-chloro-2H-benzotriazole; 2-[2′-hydroxy-5′-(2-methacryloyloxyethoxy)-3′-tert-butylphenyl]-5-methoxy-2H-benzotriazole; 2-[2′-hydroxy-5′-(gamma-methacryloyloxypropoxy)-3′-tert-butylphenyl]-5-methoxy-2H-benzotriazole; 2-(3′-t-butyl-2′-hydroxy-5′-methoxyphenyl)-5-(31-methacryloyloxypropoxy)benzotriazole or mixtures thereof.

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