Methods and compositions for the delivery of pharmaceutical agents and/or the prevention of adhesions

Abstract

The present invention provides a composition comprising one or more constitutive polymers and modifier polymers and/or hydrophilic co-surfactants useful for reducing adhesions or delivering bioactive agents. Methods for preventing and/or reducing post-surgical adhesions or delivering bioactive agents are also provided.

1 . An aqueous composition for localized delivery of a bioactive agent wherein the aqueous composition comprises a modifier polymer and a bioactive agent and the composition is applied as an aqueous composition and gels at body temperature and the release rate of the bioactive substance is altered by increasing or decreasing the concentration of modifier polymer in the aqueous composition.  
     
     
         2 . The aqueous composition of  claim 1  wherein the aqueous composition gels when in contact with the human body.  
     
     
         3 . The aqueous composition of  claim 1  wherein the aqueous composition is applied internally to tissues for the purpose of localized drug delivery.  
     
     
         4 . The aqueous composition of  claim 1  wherein the sol-gel transition temperature can be modified by addition of one or more co-surfactants.  
     
     
         5 . The aqueous composition of  claim 4  wherein the co-surfactants are hydrophilic co-surfactants.  
     
     
         6 . The aqueous composition of  claim 5  wherein the hydrophilic co-surfactants are fatty acid soaps selected from the group consisting of sodium laureate, sodium caprate, and sodium caprylate.  
     
     
         7 . The aqueous composition of  claim 5  wherein the hydrophilic co-surfactant is added at an effective concentration so as to lower the sol-gel transition temperature and provide for more rapid and complete gelation of the aqueous composition.  
     
     
         8 . The aqueous composition of  claim 5  wherein the hydrophilic co-surfactant is added at an effective concentration so as to raise the sol-gel transition temperature and provide for a less rapid and less complete gelation of the aqueous composition.  
     
     
         9 . The aqueous composition of  claim 1  wherein the bioactive agent is selected from the group consisting of antibiotics, antivirals, mydriatics, antiglaucomas, anesthetics, opthalmic agents, enzymes, cardiovascular agents, polynucleotides, genetic material, viral vectors, immunoactive agents, imaging agents, immunosuppressive agents, peptides, proteins, physiological gases, gastrointestinal agents, humectants, bactericides, bacteriostatic agents, fibrinolytic agents, agents effective in preventing leukocyte migration into the area of surgical injury and combinations thereof.  
     
     
         10 . The aqueous composition of  claim 1  wherein the modifier polymer is selected from the group consisting of cellulose ethers, sodium carboxymethylcellulose and polyacrylates.  
     
     
         11 . The aqueous composition of  claim 4  wherein the bioactive agent is selected from the group consisting of antibiotics, antivirals, mydriatrics, antiglaucomas, anesthetics, opthalmic agents, enzymes, cardiovascular agents, polynucleotides, genetic material, viral vectors, immunoactive agents, imaging agents, immunosuppressive agents, peptides, proteins, physiological gases, gastrointestinal agents, humectants, bactericides, bacteriostatic agents, fibrinolytic agents, agents effective in preventing leukocyte migration into the area of surgical injury and combinations thereof.  
     
     
         12 . The aqueous composition of  claim 1  wherein the aqueous composition can be administered using a route selected from the group consisting of topical, subcutaneous, pulmonary, synovial, intramuscular, intraperitoneal, nasal, vaginal, rectal, aural, oral and ocular.  
     
     
         13 . The aqueous composition of  claim 6  wherein the aqueous composition can be administered using a route selected from the group consisting of topical, subcutaneous, pulmonary, synovial, intramuscular, intraperitoneal, nasal, vaginal, rectal, aural, oral and ocular.  
     
     
         14 . The composition of  claim 1  wherein the modifier polymer has a molecular weight greater than or equal to 500,000.  
     
     
         15 . The composition of  claim 1  wherein the modifier is incorporated in a range between about 0.05% and 5% by weight of the composition.  
     
     
         16 . An aqueous composition for delivery of a bioactive agent wherein the aqueous composition comprises a constitutive polymer, a modifier polymer and a bactericide and the aqueous composition gels when applied to mammalian tissues wherein the sol-gel transition temperature may be altered by increasing or decreasing the concentration of a co-surfactant in the aqueous composition.  
     
     
         17 . The aqueous composition of  claim 16  wherein the co-surfactant is a fatty acid soap selected from the group consisting of sodium laureate, sodium caprate, and sodium caprylate.  
     
     
         18 . An aqueous composition for delivery of a bioactive agent wherein the aqueous composition comprises a constitutive polymer, a modifier polymer selected from the group consisting of cellulose ethers, sodium carboxymethylcellulose and polyacrylates and the aqueous composition gels when applied to mammalian tissues wherein the sol-gel transition temperature is altered by increasing or decreasing the concentration of a co-surfactant in the aqueous composition.  
     
     
         19 . The aqueous composition of  claim 18  wherein the aqueous composition further comprises a bioactive agent selected from the group consisting of antibiotics, antivirals, mydriatics, antiglaucomas, anesthetics, ophthalmic agents, enzymes, cardiovascular agents, polynucleotides, genetic material, viral vectors, immunoactive agents, imaging agents, immunosuppressive agents, peptides, proteins, physiological gases, gastrointestinal agents, humectants, bactericides, bacteriostatic agents, fibrinolytic agents, agents effective in preventing leukocyte migration into the area of surgical injury and combinations thereof.  
     
     
         20 . The aqueous composition of  claim 1  wherein increasing the concentration of modifier polymer decreases the release rate of the bioactive substance.