Ophthalmic devices for sustained delivery of active compounds

Abstract

The invention relates to an ophthalmic product which has a capability of delivering a guest material (e.g., a lubricant or a drug) in a time-controlled-releasing manner. The invention also provides a process for making an ophthalmic product of the invention. In addition, the invention provides a method for time-controlled delivery of a drug or a lubricant.

1 - 16 . (canceled) 
     
     
         17 . A process for making a soft contact lens capable of gradually delivering a guest material over an extended period of wearing time, comprising the steps of:
 a) obtaining a fluid prepolymer composition comprising an actinically-crosslinkable prepolymer and a guest material, wherein the actinically-crosslinkable prepolymer comprises ethylenically unsaturated groups and can be polymerized thermally or actinically to form the polymer matrix of the soft contact lens, wherein the guest material comprises a lubricant or a drug or both thereof, and wherein the guest material is free of any groups capable of being thermally or actinically crosslinked with the actinically-crosslinkable prepolymer, wherein the guest material is present in an amount sufficient to provide a desired functionality to the soft contact lens;   b) introducing an amount of the fluid prepolymer composition in a mold for making a contact lens;   c) polymerizing the actinically-crosslinkable prepolymer in the mold to form the soft contact lens with the guest material being not covalently linked to the polymer matrix but being distributed therein in a substantially uniform manner;   d) packaging the resultant soft contact lens in a container containing a packaging solution; and   e) sterilizing the soft contact lens in the package, wherein the sterilized soft contact lens is capable of gradually releasing the guest material during wear over at least about 6 hours, provided that the method is free of any extraction step.   
     
     
         18 . The process of  claim 17 , wherein the fluid prepolymer composition is an aqueous solution, wherein the actinically-crosslinkable prepolymer is water soluble. 
     
     
         19 . The process of  claim 17 , wherein the actinically-crosslinkable prepolymer is a water-soluble prepolymer selected from the group consisting of: a water-soluble crosslinkable poly(vinyl alcohol) prepolymer; a water-soluble vinyl group-terminated polyurethane; derivatives of a polyvinyl alcohol, polyethyleneimine or polyvinylamine; a water-soluble crosslinkable polyurea prepolymer; crosslinkable polyacrylamide; crosslinkable statistical copolymers of vinyl lactam, methyl methacrylate and a comonomer; crosslinkable copolymers of vinyl lactam, vinyl acetate and vinyl alcohol; polyether-polyester copolymers with crosslinkable side chains; branched polyalkylene glycol-urethane prepolymers; polyalkylene glycol-tetra(meth)acrylate prepolymers; crosslinkable polyallylamine gluconolactone prepolymers, and mixtures thereof. 
     
     
         20 . The process of  claim 17 , wherein the actinically-crosslinkable prepolymer is a silicone-containing prepolymer. 
     
     
         21 . The process of  claim 17 , wherein the guest material has a kinetically-unfavorable passive diffusion out of the contact lens, characterized by a ratio of eye blink-activated diffusion to passive diffusion being about 1.6 or greater, determined after a cumulative extraction period of at least about 3 hours. 
     
     
         22 . The process of  claim 21 , wherein the ratio of eye blink-activated diffusion to passive diffusion is about 2.4 or greater, determined after a cumulative extraction period of at least about 4 hours. 
     
     
         23 . The process of  claim 17 , wherein the guest material comprises a hydrophilic polymer, a mucin-like material, an ophthalmically-beneficial material, or a mixture thereof, wherein the hydrophilic polymer is a polyvinylalcohol, a polyamide, a polyimide, a polylactone, a homopolymer of a vinyl lactam, a copolymer of at least one vinyl lactam in the presence or in the absence of one or more hydrophilic vinylic comonomers, a homopolymer of acrylamide or methaacrylamide, a copolymer of acrylamide or methacrylamide with one or more hydrophilic vinylic monomers, or a mixture thereof, wherein the mucin-like material is polyglycolic acid, polylactide, collagen, gelatin, or a mixture thereof, wherein the ophthalmically-beneficial material is 2-pyrrolidone-5-carboxylic acid (PCA) or salt thereof, an amino acid or salt thereof, an alpha hydroxyl acid or salt thereof, a linoleic acid or salt thereof, a gamma linoleic acid or salt thereof, a vitamin, or a mixture thereof. 
     
     
         24 . The process of  claim 17 , wherein the number-average molecular weight M n  of the hydrophilic polymer is higher by at least 10000 than that of the actinically-crosslinkable prepolymer. 
     
     
         25 . The process of  claim 17 , wherein the guest material comprises a mixture of polyvinylalcohol and polyethylene oxide. 
     
     
         26 . The process of  claim 17 , wherein the guest material comprises a mixture of polyvinylalcohol and polyethylene oxide. 
     
     
         27 . The process of  claim 23 , wherein the hydrophilic polymer is a polyvinylalcohol, polyethylene oxide, poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam, poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone, and poly-N-vinyl4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N-N-dimethylacrylamide, polyacrylic acid, poly 2-ethyl-oxazoline, heparin polysaccharides, polysaccharides, a polyoxyethylene derivative, or a mixture thereof. 
     
     
         28 . A method for time-controlled delivery of a drug or a lubricant, comprising the steps of:
 a) obtaining a sealed package which include a packaging solution and a soft hydrogel contact lens which is obtained by cast-molding of a polymerizable composition in a mold, wherein the fluid polymerizable composition comprises a drug or lubricant without ethylenically unsaturated groups and at least one polymerizable component from the group consisting of a vinylic monomer, a macromer with one or more ethylenically unsaturated groups, an actinically-crosslinkable prepolymer with ethylenically unsaturated groups, and combinations thereof, wherein the polymer matrix of the contact lens is formed from thermal or actinic polymerization of ethylenically unsaturated groups in the polymerizable component, wherein the drug or lubricant is not covalently linked to the polymer matrix but being distributed therein, wherein the drug or lubricant is present in an amount sufficient to provide a desired functionality to the contact lens, and wherein the drug or lubricant is characterized by a ratio of eye blink-activated diffusion to passive diffusion being about 1.6 or greater, determined after a cumulative extraction period of at least about 3 hours;   b) wearing the soft hydrogel contact lens in an eye; and   c) gradually delivering, under eye blinks, the drug or lubricant during wear over at least about 6 hours.   
     
     
         29 . The method of  claim 28 , wherein the polymerizable composition is a prepolymer composition comprising an actinically-crosslinkable prepolymer and the soft hydrogel contact lens is produced in a manufacturing process without any extraction steps. 
     
     
         30 . The method of  claim 28 , wherein the ratio of eye blink-activated diffusion to passive diffusion is about 2.4 or greater, determined after a cumulative extraction period of at least about 4 hours. 
     
     
         31 . The method of  claim 17 , wherein the actinically-crosslinkable prepolymer is a polyhydroxyl compound having a molecular weight of at least about 2000 and comprising from about 0.5 to about 80%, based on the number of hydroxyl groups in the poly(vinyl alcohol), of units of the formula I, I and II, I and III, or I and II and III 
       
         
           
           
               
               
           
         
       
       in which
 the molecular weight refers to a weight average molecular weight, Mw, determined by gel permeation chromatography, 
 R is linear or branched alkylene having up to 12 carbon atoms, 
 R 1  is hydrogen or lower alkyl having up to seven, 
 R 2  is an ethylenically unsaturated, electron-withdrawing, crosslinkable radical having up to 25 carbon atoms, 
 R 3  is hydrogen, a C 1 -C 6  alkyl group or a cycloalkyl group, 
 R 7  is a primary, secondary, tertiary amino group, or a quaternary amino group of the formula N + (R′) 3 X − , in which each R′, independently of the others, is hydrogen or a C 1 -C 4  alkyl radical and X is a counterion, 
 R 8  is the radical of a monobasic, dibasic or tribasic, saturated or unsaturated, aliphatic or aromatic organic acid or sulfonic acid.