Lactam polymer derivatives

Abstract

Lactam polymers has been modified with sodium borohydride (NaBH 4 ) to yield lactam polymers bearing hydroxyl functional groups. These functional groups are useful for the covalent attachment of reactive groups, fluorescent probes, antimicrobial agents, bioactive factors, and drugs. The resulting as components for medical devices, specifically ophthalmic devices and more specifically contact lenses. Hydrogels based on these polymers are also useful for biomedical applications in the areas of drug delivery, tissue engineering, and implantable devices.

1 - 25 . (canceled)  
     
     
         26 . A process comprising reacting in a solvent at least one lactam polymer and a reducing agent to form a hydroxyl functionalized lactam polymer derivative and reacting said hydroxyl functionalized lactam polymer derivative with a polymerizable reagent comprising at least one polymerizable group to form a reactive lactam polymer.  
     
     
         27 . The process of  claim 26  wherein said polymerizable group is selected from the group consisting of acrylates, styryls, vinyls, vinyl ethers, C1-6alkylacrylates, acrylamides, C1-6alkylacrylamides, N-vinyllactams, N-vinylamides, C2-12alkenyls, C2-12alkenylphenyls, C2-12alkenylnaphthyls, or C2-6alkenylphenylC1-6alkyls, vinyl ethers, epoxide groups and combinations thereof.  
     
     
         28 . The process of  claim 26  wherein said polymerizable group is selected from the group consisting of methacrylates, acrylates, methacrylamides, acrylamides, and combinations thereof.  
     
     
         29 . The process of  claim 26  wherein said polymerizable reagent is selected from the group consisting of reagents include acryloyl chloride, methacryloyl chloride, methacrylic anhydride, methacrylic acid, acrylic acid, 3-isopropenyl-alpha, alpha-dimethylbenzyl isocyanate, 2-isocyanatoethyl methacrylate and combinations thereof.  
     
     
         30 . The process of claim  1  further comprising the step of reacting said hydroxyl functionalized lactam polymer derivative with a reactive fluorescent dye to form a fluorescently labeled lactam polymer.  
     
     
         31 . The process of  claim 30  wherein said reactive fluorescent dye is selected from the group consisting of Texas Red, N-methylisatoic anhydride, dansyl derivatives, rhodamine derivatives, fluorescein derivatives, anthracene derivatives, carbazole derivatives, coumarin derivatives and combinations thereof.  
     
     
         32 . The process of  claim 32  wherein said reactive fluorescent dye is selected from the group consisting of dansyl chloride, dansyl hydrazine, m-dansylaminophenylboronic acid, tetramethylrhodamine-5-carbonyl azide, fluorescein (free acid and sodium salt), fluorescein isothiocyanate (FITC), 5-(4,6-dichlorotriazinyl)aminofluorescein (5-DTAF), fluorescamine, fluorescein-5-carbonyl azide diacetate, 9-anthroyInitrile, 9-anthracene carbonyl chloride, 9-carbazoleacetic acid, carbazole-9-carbonyl chloride, 9-carbazolepropionic acid, 7-diethylaminocoumarin-3-carbonyl azide, 7-methoxycoumarin-3-carbonyl azide and combinations thereof.  
     
     
         33 . The process of  claim 26  or  30  wherein said polymerizable reagent or fluorescent dye is present in an amount from about 0.001 to 50 weight percent, based on number of hydroxyl functional groups in the hydroxyl functionalized lactam polymer derivative.  
     
     
         34 . The process of  claim 26  or  30  wherein said polymerizable reagent or fluorescent dye is present in an amount from about 0.001 to 25 weight percent, based on number of hydroxyl functional groups in the hydroxyl functionalized lactam polymer derivative.  
     
     
         35 . The process of  claim 26  or  30  wherein said polymerizable reagent or fluorescent dye is present in an amount from about 0.001 to 15 weight percent, based on number of hydroxyl functional groups in the hydroxyl functionalized lactam polymer derivative.  
     
     
         36 . The process of  claim 26  wherein said polymerizable reagent comprises a biologically active agent.  
     
     
         37 . The process of  claim 36  wherein biologically active agent comprises a hydroxyl reactive compound selected from the group consisting of ACE-inhibitors; anti-anginal drugs; anti-arrhythmias; anti-asthmatics; anti-cholesterolemics; anti-convulsants; anti-depressants; anti-diarrhea preparations; anti-histamines; anti-hypertensive drugs; anti-infectives; anti-inflammatory agents; anti-lipid agents; anti-manics; anti-nauseants; anti-stroke agents; anti-thyroid preparations; anti-tumor drugs; anti-tussives; anti-uricemic drugs; anti-viral agents; acne drugs; alkaloids; amino acid preparations; anabolic drugs; analgesics; anesthetics; angiogenesis inhibitors; antacids; anti-arthritics; antibiotics; anticoagulants; antiemetics; antiobesity drugs; antiparasitics; antipsychotics; antipyretics; antispasmodics; antithrombotic drugs; anxiolytic agents; appetite stimulants; appetite suppressants; beta blocking agents; bronchodilators; cardiovascular agents; cerebral dilators; chelating agents; cholecystokinin antagonists; chemotherapeutic agents; cognition activators; contraceptives; coronary dilators; cough suppressants; decongestants; deodorants; dermatological agents; diabetes agents; diuretics; emollients; enzymes; erythropoietic drugs; expectorants; fertility agents; fungicides; gastrointestinal agents; growth regulators; hormone replacement agents; hyperglycemic agents; hypnotics; hypoglycemic agents; laxatives; migraine treatments; mineral supplements; mucolytics; narcotics; neuroleptics; neuromuscular drugs; NSAIDS; nutritional additives; peripheral vasodilators; prostaglandins; psychotropics; renin inhibitors; respiratory stimulants; steroids; stimulants; sympatholytics; thyroid preparations; tranquilizers; uterine relaxants; vaginal preparations; vasoconstrictors; vasodilators; vertigo agents; vitamins; wound healing agents and combinations thereof.  
     
     
         38 . The process of  claim 37  wherein said biologically active agent is a carboxylic acid derivative.  
     
     
         39 . The process of  claim 26  wherein said polymerizable reactive agent is at least one reactive moiety selected from the group consisting of carbamates, acyl chlorides, sulfonyl chlorides, isothiocyanates, cyanoacrylates, oxiranes, imines, thiocarbonates, thiols, aldehydes, aziridines, azides and combinations thereof; and said reactive lactam polymer is a moisture curable polymer.  
     
     
         40 . The process of  claim 39  wherein said reacting step is conducted in at least one anhydrous solvent.  
     
     
         41 . A polymer comprising substituted and unsubstituted lactam repeating units and hydroxy alkyl substituted amine repeating units in said polymer's backbone.  
     
     
         42 . The polymer of  claim 41  wherein said hydroxy alkyl substituted amine repeating units are randomly distributed throughout said polymer backbone.  
     
     
         43 . The polymer of  claim 41  wherein said hydroxy alkyl substituted amine repeating units comprise about 1 to about 20 mol percent of the lactam groups  
     
     
         44 . The polymer of  claim 41  wherein said lactam repeating units comprise at least about 10% of said polymer's repeating units.  
     
     
         45 . The polymer of  claim 41  wherein said lactam repeating units comprise at least about 30% of said polymer's repeating units.  
     
     
         46 . The polymer of  claim 41  wherein said lactam repeating units polymer comprise at least about 50% of said polymer's repeating units.  
     
     
         47 . The polymer of  claim 41  wherein said at least one lactam group is selected from the group consisting of substituted and unsubstituted 4 to 7 membered lactam rings.  
     
     
         48 . The polymer of  claim 41  wherein said at least one lactam group is selected from the group consisting of unsubstituted 4 to 6 membered lactam rings.  
     
     
         49 . The polymer of  claim 41  wherein said at least one lactam group is selected from the group consisting of N-vinyl-2-pyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-3-methyl-2-piperidone, N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-pyrrolidone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-5-methyl-2-pyrrolidone, N-vinyl-5-methyl-2-piperidone, N-vinyl-5,5-dimethyl-2-pyrrolidone, N-vinyl-3,3,5-trimethyl-2-pyrrolidone, N-vinyl-5-methyl-5-ethyl-2-pyrrolidone, N-vinyl-3,4,5-trimethyl-3-ethyl-2-pyrrolidone, N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone, N-vinyl-3,5-dimethyl-2-piperidone, N-vinyl-4,4-dimethyl-2-piperidone, N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam, N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl-4,6-dimethyl-2-caprolactam, N-vinyl-3,5,7-trimethyl-2-caprolactam, N-vinylmaleimide, vinylsuccinimide and mixtures thereof.  
     
     
         50 . The polymer of  claim 41  wherein said at least one lactam group comprises N-vinyl-2-pyrrolidone.  
     
     
         51 . The polymer of  claim 41  wherein said lactam polymer further comprises repeat units derived from at least one comonomer.  
     
     
         52 . The polymer of  claim 51  wherein said at least one comonomer is selected from the group consisting of methyl methacrylate, methacrylic acid, styrene, butadiene, acrylonitrile, 2-hydroxyethylmethacrylate, acrylic acid, methyl acrylate, methyl methacrylate, vinyl acetate, N,N-dimethylacrylamide, N-isopropylacrylamide and polyethyleneglycol monomethacrylates and combinations thereof.  
     
     
         53 . The polymer of  claim 51  wherein said at least one comonomer is selected from the group consisting of methacrylic acid, acrylic acid, acetonitrile and mixtures thereof.  
     
     
         54 . A hydrogel formed from a reaction mixture comprising at least one hydrophilic monomer and a lactam component selected from the group consisting of hydroxyl functionalized lactam polymers, reactive lactam polymers, fluorescently labeled lactam polymers and combinations thereof.  
     
     
         55 . The hydrogel of  claim 54  wherein said reaction mixture further comprises at least one silicone containing component.  
     
     
         56 . A biomedical device comprising the hydrogel of  claim 54 .  
     
     
         57 . The biomedical device of  claim 56 , wherein said device is selected from the group consisting of catheters, implants, stents, bioadhesives, sealants and ophthalmic devices.  
     
     
         58 . The biomedical device of  claim 56 , wherein said device is a contact lens.