Hydroswellable, Segmented, Aliphatic Polyurethanes and Polyurethane Ureas

Abstract

Hydroswellable, absorbable and non-absorbable, aliphatic, segmented polyurethanes and polyurethane-urea capable of swelling in the biological environment with associated increase in volume of at least 3 percent have more than one type of segments, including those derived from polyethylene glycol and the molecular chains are structurally tailored to allow the use of corresponding formulations and medical devices as carriers for bioactive agents, rheological modifiers of cyanoacrylate-based tissue adhesives, as protective devices for repairing defective or diseased components of articulating joints and their cartilage, and scaffolds for cartilage tissue engineering.

1 . A hydroswellable, segmented, aliphatic polyurethane composition comprising polyoxyalkylene chains covalently linked to a second group of polymeric chain segments, the second group of chain segments selected from the group consisting of polyalkylene carbonate chains and polyester chains, the second group of chain segments interlinked with a third group of chain segments, the third group of chain segments selected from the group consisting of aliphatic urethane segments and aliphatic urea segments, the composition exhibiting at least 3 percent increase in volume when placed in the biological environment. 
   
   
       2 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 1  wherein the polyoxyalkylene chains comprise at least one type of oxyalkylene sequences selected from the group consisting of oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene sequences and the second group of chain segments comprise alkylene carbonate chains comprising trimethylene carbonate sequences. 
   
   
       3 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 2  wherein the third group of chain segments comprise aliphatic urethane segments derived from at least one diisocyanate selected from the group consisting of tetramethylene diisocyanate, hexamethylene diisocyanate, octamethylene diisocyanate, decamethylene diisocyanate, dodecamethylene diisocyanate, lysine-derived diisocyanate, and cyclohexane bis-(methylene isocyanate). 
   
   
       4 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 1  as a component of a vehicle for a controlled release formulation of at least one bioactive agent selected from the group consisting of anti-inflammatory agents, anesthetic agents, cell growth promoting agents, antimicrobial agents, antiviral agents, and antineoplastic agents. 
   
   
       5 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 4  wherein the controlled release formulation comprises at least one antimicrobial agent for treating periodontitis or bone infection selected from the group consisting of doxycycline, gentamicin, vancomycin, tobramycin, clindamycin, and mitomycin. 
   
   
       6 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 4  wherein the controlled release formulation comprises an excipient selected from the group consisting of liquid polyethylene glycol, an alkylated polyethylene glycol derivative, and an acylated polyethylene glycol derivative and at least one bioactive agent selected from the group consisting of paclitaxel, carboplatin, miconazole, leflunamide, ciprofloxacin, and a recombinant protein for treating breast or ovarian cancer in humans or animals. 
   
   
       7 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 1  admixed with at least one cyanoacrylate monomer for use as a rheological modifier of tissue adhesives. 
   
   
       8 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 1  wherein the polyoxyalkylene chains comprise at least one type of oxyalkylene sequences selected from the group consisting of oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene sequences and wherein the second group of chain segments comprise urethane segments derived from at least one diisocyanate selected from the group consisting of hexamethylene diisocyanate, hexamethylene diisocyanate, octamethylene diisocyanate, decamethylene diisocyanate, dodecamethylene diisocyanate, 1,4 cyclohexane diisocyanate, lysine-derived diisocyanate, and cyclohexane bis(methylene isocyanate), and wherein the resulting polyoxyalkylene urethane molecules having at least one isocyanate terminal group are chain-extended with an alkylene diamine selected from the group consisting of ethylene-, trimethylene-, tetramethylene-, hexamethylene-, and octamethylene-diamine, thereby forming polyetherurethane-urea segmented chains. 
   
   
       9 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 8  for use as an artificial cartilage to restore the function of diseased or defective articulating joints in humans and animals. 
   
   
       10 . A hydroswellable, segmented, aliphatic polyurethane composition as in  claim 1  wherein the second set of chain segments comprise polyester chain segments, the polyester chain segments selected from the group consisting of polyester-carbonate chain segments and polyester chain segments derived from at least one cyclic monomer selected from the group consisting of ε-caprolactone, trimethylene carbonate, p-dioxanone, 1,5-dioxepan-2-one, l-lactide, dl-lactide, glycolide, and a morpholinedione. 
   
   
       11 . A hydroswellable, segmented, aliphatic-polyurethane composition as in  claim 10  exhibiting microporosity with an essentially continuous cellular structure for an absorbable scaffold or part thereof for cartilage tissue engineering. 
   
   
       12 . A hydroswellable, segmented, aliphatic polyurethane-urea composition comprising a combination of linear functionalized polysiloxane and polyoxyalkylene chains interlinked with urethane segments, wherein the polyalkylene urethane segments are further interlinked with aliphatic urea chain segments, the composition exhibiting at least 5 percent increase in volume when placed in the biological environment upon using as an artificial cartilage to restore the function of diseased or defective articulating joints in humans and animals. 
   
   
       13 . A hydroswellable, segmented aliphatic polyurethane-urea composition as in  claim 12  wherein the polyoxyalkylene chains comprise at least one type of oxyalkylene sequences selected from the group consisting of oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene sequences and the functionalized polysiloxane is derived from bis-hydroxyalkyl-terminated polysiloxane comprising at least dimethoxysiloxane internal sequences and two hydroxyalkyl or aminoalkyl terminals and further wherein the urethane segments are derived from at least one diisocyanate selected from the group consisting of hexamethylene diisocyanate, octamethylene diisocyanate, decamethylene diisocyanate, dodecamethylene diisocyanate, 1,4 cyclohexane diisocyanate, lysine-derived diisocyanate, and cyclohexane bis(methylene isocyanate) and wherein the resulting polyoxyalkylene urethane molecules having at least one isocyanate terminal group are further chain-extended with an alkylene diamine selected from the group consisting of ethylene-, trimethylene-, tetramethylene-, hexamethylene-, and octamethylene-diamine, thereby forming polyetherurethane-urea segmented chains.