Bioactive polymeric liquid formulations of absorbable, segmented aliphatic polyurethane compositions

Abstract

Bioactive liquid formulations are formed of combinations of absorbable, segmented aliphatic polyurethane compositions and liquid polyether for use as vehicles for the controlled release of at least one active agent for the conventional and unconventional treatment of different forms of cancer and the management of at least one type of bacterial, fungal, and viral infection.

What is claimed is: 
     
         1 . A bioactive polymeric liquid formulation comprising a blend of an absorbable, segmented, aliphatic polyurethane, a liquid polyoxyalkylene and at least one drug selected from the group consisting of doxycycline, mitomycin, clindamycin, miconazole, clotrimazole, ketoconazole, fluconazole, butoconazole, tioconazole, leflunomide, 5-fluorouracil, paclitaxel, carboplatin, mycophenolic acid, podophyllinic acid, podophyllotoxin and related bioactive compounds. 
     
     
         2 . A bioactive polymeric liquid formulation as in  claim 1  wherein the liquid polyoxyalkylene comprises chains comprising at least one type of oxyalkylene sequence selected from the group consisting of oxyethylene, oxypropylene, and oxytrimethylene. 
     
     
         3 . A bioactive polymeric liquid formulation as in  claim 1  comprising polyoxyalkylene chains covalently linked to alkylene carbonate chains, wherein the polyalkylene carbonate chains are interlinked with aliphatic urethane segments. 
     
     
         4 . A bioactive polymeric liquid formulation as in  claim 3  wherein the alkylene carbonate chains comprise trimethylene carbonate sequences and the aliphatic urethane segments are derived from at least one diisocyanate selected from the group consisting of tetramethylene diisocyanate, hexamethylene diisocyanate, lysine-derived diisocyanate, and cyclohexane bis (methylene isocyanate). 
     
     
         5 . A bioactive polymeric liquid formulation as in  claim 3  wherein the segmented polyurethane is made by the method comprising the steps of end-grafting polyethylene glycol having a molecular weight of about 400 Da with trimethylene carbonate, and interlinking the end-grafted polyethylene glycol with hexamethylene diisocyanate. 
     
     
         6 . A bioactive polymeric liquid formulation as in  claim 5  as a vehicle for the controlled release of at least one antineoplastic agent for treating at least one type of cancer selected from breast, ovarian, cervical, lung, prostate, testicular, and skin cancer. 
     
     
         7 . A bioactive polymeric liquid formulation as in  claim 6  wherein the at least one antineoplastic agent is selected from the group consisting of paclitaxel, 5-fluorouracil, podophyllinic acid, mycophenolic acid, and carboplatin. 
     
     
         8 . A bioactive polymeric liquid formulation as in  claim 6  wherein the at least one antineoplastic agent is selected from antimicrobial agents and immunosuppressant agents selected from the group consisting of doxycycline, tetracycline, mitomycin, clindamycin, miconazole, ketoconazole, fluconazole, and leflunomide. 
     
     
         9 . A bioactive polymeric liquid formulation as in  claim 5  as a vehicle for the controlled release of at least one antifungal agent for treating vaginal yeast, nail and skin fungal infections, the agent selected from the group consisting of miconazole, ketoconazole, butoconazole, clotrimazole. 
     
     
         10 . A bioactive polymeric liquid formulation as in  claim 5  as a vehicle for the controlled release of at least one antibacterial agent for treating vaginal and skin bacterial infections, the agent selected from the group consisting of doxycycline, mitomycin, and clindamycin. 
     
     
         11 . A bioactive polymeric liquid formulation as in  claim 5  as a vehicle for the controlled release of at least one antibacterial agent for treating periodontitis and related dental infections, the agent selected from the group consisting of doxycycline, tetracycline, clindamycin, and mitomycin. 
     
     
         12 . A bioactive polymeric liquid formulation as in  claim 5  as a vehicle for the controlled release of at least one agent for treating genital, nail, and skin warts, and related infections, the agent selected from the group consisting of paclitaxel, 5-fluorourecil, podophyllinic acid, podophyllotoxin, miconazole, ketoconazole, butoconazole, fluconazole, and clotrimazole. 
     
     
         13 . A bioactive polymeric liquid formulation as in  claim 1  comprising an aliphatic polyurethane-urea comprising polyoxyalkylene chains covalently linked to polyalkylene-urethane chains wherein the polyalkylene-urethane chains are further interlinked with aliphatic urea chain segments. 
     
     
         14 . A bioactive polymeric liquid formulation as in  claim 13  wherein the polyoxyalkylene chains comprise at least one type of oxyalkylene sequence selected from the group consisting of oxyethylene, oxypropylene, and oxytrimethylene and the urethane chain segments are derived from at least one diisocyanate selected from the group consisting of hexamethylene 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-, and hexamethylene-diamine, thereby forming polyurethane-urea segmented chains. 
     
     
         15 . A bioactive polymeric liquid formulation as in  claim 14  as a vehicle for the controlled release of at least one antineoplastic agent for treating at least one type of cancer selected from breast, ovarian, cervical, lung, prostate, testicular, and skin cancer. 
     
     
         16 . A bioactive polymeric liquid formulation as in  claim 15  wherein the at least one antineoplastic agent is selected from the group consisting of paclitaxel, 5-fluorouracil, podophyllinic acid, mycophenolic acid, and carboplatin. 
     
     
         17 . A bioactive polymeric liquid formulation as in  claim 15  wherein the at least one antineoplastic agent is selected from antimicrobial agents and immunosuppressant agents selected from the group consisting of doxycycline, tetracycline, mitomycin, clindamycin, miconazole, ketoconazole, fluconazole, and leflunomide. 
     
     
         18 . A bioactive polymeric liquid formulation as in  claim 1  comprising a polyether-ester-urethane comprising polyoxyalkylene chains covalently linked to polyester chain segments, wherein the polyester chains are interlinked with aliphatic urethane segments. 
     
     
         19 . A bioactive polymeric liquid formulation as in  claim 18  wherein the polyester chain segments comprise polyester-carbonate chain segments. 
     
     
         20 . A bioactive polymeric liquid formulation as in  claim 19  wherein the polyester chain segments are derived from at least one cyclic monomer selected from the group consisting of ε-caprolactone, p-dioxanone, 1,5-dioxepan-2-one, trimethylene carbonate, l-lactide, glycolide, dl-lactide, and a morpholinedione. 
     
     
         21 . A bioactive polymeric liquid formulation as in  claim 20  as a vehicle for the controlled release of at least one antineoplastic agent for treating at least one type of cancer selected from breast, ovarian, cervical, lung, prostate, testicular, and skin cancer. 
     
     
         22 . A bioactive polymeric liquid formulation as in  claim 21  wherein the at least one antineoplastic agent is selected from the group consisting of antineoplastic agents consisting of paclitaxel, 5-fluorouracil, podophyllinic acid, mycophenolic acid, and carboplatin. 
     
     
         23 . A bioactive polymeric liquid formulation as in  claim 21  wherein the at least one antineoplastic agent is selected from antimicrobial agents and immunosuppressant agents selected from the group consisting of doxycycline, tetracycline, mitomycin, clindamycin, miconazole, ketoconazole, fluconazole, and leflunomide. 
     
     
         24 . A bioactive polymeric liquid formulation as in  claim 20  as a vehicle for the controlled release of at least one antibacterial agent for treating periodontitis and related dental infections, the agent selected from the group consisting of doxycycline, tetracycline, clindamycin, and mitomycin. 
     
     
         25 . A bioactive polymeric liquid formulation as in  claim 20  as a vehicle for the controlled release of at least one agent for treating fungus-infected nails and genital and skin warts, and related infections, the agent selected from the group consisting of paclitaxel, 5-fluorourecil, podophyllinic acid, podophyllotoxin, miconazole, ketoconazole, butoconazole, fluconazole, and clotrimazole.