Drug dispensing wound dressing

Abstract

The disclosed wound dressings have a drug dispersed throughout a polyurethane matrix that is the reaction product of: (A) An isocyante terminated prepolymer formed by reaction of isophorone diisocyanate and a marcoglycol and (B) a monomer containing hydroxyl and vinyl groups. The reaction product is a vinyl terminated polyurethane oligomer which is liquid at room temperature and which may be readily admixed with a pharmacoactive substance and a photosensitizer, formed into a film and cured by exposure to UV light without release of heat. In the most preferred embodiments the foregoing oligomer is codissolved in an organic solvent with a polyurethane polymer which is the reaction product of: dicyclohexyl methane diisocyanate; a polytetramethylene ether polyol having a molecular weight in the range of 1000-3000 daltons; and 1,4-butane diol. That solution is then admixed with the pharmacoactive agent, formed into a film and cured.

What is claimed is: 
     
       1. A wound dressing comprising a drug-dispensing elastomeric film, said film comprising: A. A cured reaction product consiting essentially of: (1) isophorone diisocyanate;   (2) a macroglycol; and   (3) a monomer containing hydroxyl and vinyl groups; and     B. a pharmacoactive agent dispersed through said cured reaction product.   
     
     
       2. The cured wound dressing of claim 1 wherein the repeating molecular units of said film are cross-linked through terminal vinyl groups. 
     
     
       3. The wound dressing of claim 1 wherein said film has been cured by incorporation of a photosensitizer and exposure to ultraviolet light. 
     
     
       4. The wound dressing of claim 1 wherein said reaction product is formed by: (a) reacting said isophorone diisocyanate and said macroglycol together in the presence of a catalyst to form an isocyanate terminated prepolymer;   (b) reacting said prepolymer with said monomer containing hydroxyl and vinyl groups to form an ultraviolet-curable, vinyl terminated polyurethane oligomer;   (c) admixing said oligomer with the pharmacoactive agent to form an UV-curable homogeneous blend;   (d) forming the UV-curable homogeneous mixture into a film; and   (e) curing said film by exposure to ultraviolet light.   
     
     
       5. The wound dressing of claim 4 wherein said macroglycol is polypropylene glycol having a number average molecular weight of 500-5000 daltons and said monomer is hydroxyethyl methacrylate. 
     
     
       6. The wound dressing of claim 4 wherein said film contains 1-10 wt. % of said drug, based on the weight of said oligomer. 
     
     
       7. The wound dressing of claim 4 wherein said drug is selected from the group consisted of coagulants, antibiotics, antifungals, topical anesthetics, anti-inflammatories mixtures thereof. 
     
     
       8. The wound dressing of claim 4 further comprising a coating of a pressure sensitive adhesive on one surface of said film. 
     
     
       9. The wound dressing of claim 4 wherein a photoinitiator is admixed with said oligomer. 
     
     
       10. The wound dressing of claim 9 wherein said photoinitiator is selected from the group consisting of diacetoxyacetobenzophenone, benzophenone, diethoxyacetophenone 4-morpholine benzophenone, 4-aminobenzophenone and 4'-methoxyacetophenone. 
     
     
       11. The wound dressing of claim 4 wherin said film further comprises at least one non-reactive thixotropic agent. 
     
     
       12. The wound dressing of claim 11 wherein said non-reactive thixotropic agent is selected from the group consisting of pyrogenic silica and bentonite clays. 
     
     
       13. The wound dressing of claim 4 wherein the vinyl terminated oligomer is co-dissolved with a polyurethane polymer which is the reaction product of: (d) dicyclohexyl methane diisocyanate;   (e) a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 Daltons; and   (f) 1,4-butane diol; and the resulting solution is formed into said film.     
     
     
       14. The wound dressing of claim 13 wherein said film contains 80-99 parts by weight of said vinyl terminated oligomer and 1-20 parts by weight of said polyurethane polymer. 
     
     
       15. The wound dressing of claim 13 further comprising a textile fabric, said film being formed on said textile fabric. 
     
     
       16. The wound dressing of claim 15 wherein said textile fabric is first coated with a polyurethane polymer that is the reaction product of: dicyclohexyl methane diisocyanate;   a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 Daltons; and   1,4-butane diol and then coated with said solvent solution.     
     
     
       17. The wound dressing of claim 16 further comprising a coating of a pressure sensitive adhesive on one surface of said film. 
     
     
       18. The wound dressing of claim 13 wherin said film further comprises at least one non-reactive thixotropic agent. 
     
     
       19. The wound dressing of claim 18 wherein said non-reactive thixotropic agent is selected from the group consisting of pyrogenic silica and bentonite clays. 
     
     
       20. A process for forming a drug-dispensing wound dressing comprising: (1) preparing a reaction product consisting essentially of isophorone diisocyanate, a macroglycol and a monomer containing hydroxyl and vinyl groups by reacting (a) isophorone diisocyanate and   (b) a macroglycol in the presence of a catalyst to form an isocyanate terminated prepolymer and   reacting said prepolymer with (c) a monomer containing hydroxyl and vinyl groups to form an ultraviolet-curable, vinyl terminated polyurethane liquid oligomer;   (2) admixing said vinyl terminated oligomer with a drug to form an UV-curable mixture;   (3) forming the UV-curable mixture into a film; and   (4) curing said film by exposure to ultraviolet light.   
     
     
       21. The process of claim 20 wherein a photoinitiator is admixed with said oligomer and wherein said curing is at approximately room temperature. 
     
     
       22. The process of claim 20 wherein said macroglycol is polypropylene glycol having a number average molecular weight of 500-5000 daltons and said monomer is hydroxyethyl methacrylate. 
     
     
       23. The process of claim 20 wherein said drug is added in an amount 1-10% by weight, based on the weight of said oligomer. 
     
     
       24. The process of claim 20 wherein said drug is selected from the group consisting of coagulants, antibiotics, antifungals, topical anesthetics, amti-inflammatories and mixtures thereof. 
     
     
       25. The process of claim 20 further comprising coating one surface of said film with a pressure sensitive adhesive. 
     
     
       26. The process of claim 21 wherein said photoinitiator is selected from the group consisting of diacetoxyacetobenzophenone, benzophenone, diethoxyacetophenone, 4-morpholine benzophenone, 4-aminobenzophenone and 4'-methoxyacetophenone. 
     
     
       27. The process of claim 21 further comprising mixing said oligomer with at least one non-reactive thixotropic agent. 
     
     
       28. The process of claim 27 wherein said non-reactive thixotropic agent is selected from the group consisting of pyrogenic silica and bentonite clays. 
     
     
       29. A process in accordance with claim 20 wherein said vinyl terminated oligomer is dissolved in an organic solvent and the drug is admixed in said solvent solution. 
     
     
       30. A process in accordance with claim 29 wherein the vinyl terminated oligomer is co-dissolved with a polyurethane polymer which is the reaction product of: (d) dicyclohexyl methane diisocyanate;   (e) a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 daltons; and   (f) 1,4-butane diol.   
     
     
       31. The process of claim 30 wherein 80-99 parts by weight of said vinyl terminated oligomer are codissolved with 1-20 parts by weight of said polyurethane polymer. 
     
     
       32. The process of claim 30 wherein said monomer is hydroxyethyl methacrylate and said macroglycol is a polypropylene glycol having a number average molecular weight of 500-3000 daltons. 
     
     
       33. The process of claim 30 further comprising providing a textile fabric and coating said textile fabric with said solvent solution to form said film. 
     
     
       34. The process of claim 33 wherin said textile fabric is first coated with a polyurethane polymer that is the reaction product of: dicyclohexyl methane diisocyanate;   a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 daltons; and   
     
     
       1. 4-butane diol and then coated with said solvent solution.   
     
     
       35. A process in accordance with claim 20 wherein a sufficient amount of (c) is added so that only compounds with number average molecular weights of 1500-5000 are present. .Iadd. 
     
     
       36.  A dispensing elastomeric film, said film comprising: A. A cured reaction product consisting essentially of: (1) isophorone diisocyanate;   (2) a macroglycol; and   (3) a monomer containing hydroxyl and vinyl groups; and     B. an agent to be dispensed through said cured reaction product. .Iaddend. .Iadd.37. The cured dispensing elastomeric film of claim 36 wherein the repeating molecular units of said film are cross-linked through terminal   
     
     
        vinyl groups. .Iaddend. .Iadd.38.  The dispensing elastomeric film of claim 36 wherein said film has been cured by incorporation of a photosensitizer and exposure to ultraviolet light. .Iaddend. .Iadd.39. The dispensing elastomeric film of claim 36 wherein said reaction product is formed by: (a) reacting said isophorone diisocyanate and said macroglycol together in the presence of a catalyst to form an isocyanate terminated prepolymer;   (b) reacting said prepolymer with said monomer containing hydroxyl and vinyl groups to form an ultraviolet-curable, vinyl terminated polyurethane oligomer;   (c) admixing said oligomer with the agent to be dispensed to form an UV-curable homogeneous blend;   (d) forming the UV-curable homogeneous mixture into a film; and   (e) curing said film by exposure to ultraviolet light. .Iaddend. .Iadd.40. The dispensing elastomeric film of claim 39 wherein said macroglycol is polypropylene glycol having a number average molecular weight of 500-5000 daltons and said monomer is hydroxyethyl methacrylate. .Iaddend. .Iadd.41. The dispensing elastomeric film of claim 39 wherein said film containing 1-10 wt. % of said agent to be dispensed, based on the weight of said oligomer. .Iaddend. .Iadd.42. The dispensing elastomeric film of claim 39 further comprising a coating of a pressure sensitive adhesive on one surface of said film. .Iaddend. .Iadd.43. The dispensing elastomeric film of claim 39 wherein a photoinitiator is admixed with said oligomer. .Iaddend. .Iadd.44. The dispensing elastomeric film of claim 43 wherein said photoinitiator is selected from the group consisting of diacetoxyacetobenzophenone, benzophenone, diethoxyacetophenone 4-morpholine benzophenone, aminobenzophenone and 4'-methoxyacetophenone. .Iaddend. .Iadd.45. The dispensing elastomeric film of claim 39 wherein said film further comprises at least one non-reactive thixotropic agent. .Iaddend. .Iadd.46. The dispensing elastomeric film of claim 45 wherein said non-reactive thixotropic agent is selected from the group consisting of pyrogenic silica and bentonite clays. .Iaddend. .Iadd.47. The dispensing elastomeric film of claim 39 wherein the vinyl terminator oligomer is co-dissolved with a polyurethane polymer which is the reaction product of:   (d) dicyclohexyl methane diisocyanate;   (e) a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 Daltons; and   (f) 1,4-butane diol;   and the resulting solution is formed into said film. .Iaddend. .Iadd.48. The dispensing elastomeric film of claim 47 wherein said film contains 80-99 parts by weight of said vinyl terminated oligomer and 1-20 parts by weight of said polyurethane polymer. .Iaddend. .Iadd.49. The dispensing elastomeric film of claim 47 further comprising a textile fabric, said film being formed on said textile fabric. .Iaddend. .Iadd.50. The dispensing elastomeric film of claim 49 wherein said textile fabric is first coated with a polyurethane polymer that is the reaction product of:   dicyclohexyl methane diisocyanate;   a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 Daltons; and   1,4-butane diol   and then coated with said solvent solution. .Iaddend. .Iadd.51. The dispensing elastomeric film of claim 50 further comprising a coating of a pressure sensitive adhesive on one surface of said film. .Iaddend. .Iadd.52. The dispensing elastomeric film of claim 47 wherein said film further comprises at least one non-reactive thixotropic agent. .Iaddend. .Iadd.53. The dispensing elastomeric film of claim 52 wherein said non-reactive thixotropic agent is selected from the group consisting of pyrogenic silica and bentonite clays. .Iaddend. .Iadd.54. A process for forming and dispensing elastomeric film comprising:   (1) preparing a reaction product consisting essentially of isophorone diisocyanate, a macroglycol and a monomer containing hydroxyl and vinyl groups by reacting (a) isophorone diisocyanate and (b) a macroglycol in the presence of a catalyst to form an isocyanate terminated prepolymer and reacting said prepolymer with (c) a monomer containing hydroxyl and vinyl groups to form an ultraviolet-curable, vinyl terminated polyurethane liquid oligomer;   (2) admixing said vinyl terminated oligomer with an agent to be dispensed to form an UV-curable mixture;   (3) forming the UV-curable mixture into a film; and   (4) curing said film by exposure to ultraviolet light. .Iaddend. .Iadd.55. The process of claim 54 wherein a photoinitiator is admixed with said oligomer and wherein said curing is at approximately room temperature. .Iaddend. .Iadd.56. The process of claim 54 wherein said macroglycol is polypropylene glycol having a number average molecular weight of 500-5000 daltons and said monomer is hydroxyethyl methacrylate. .Iaddend. .Iadd.57. The process of claim 54 wherein said agent is added in an amount 1-10% by weight, based on the weight of said oligomer. .Iaddend. .Iadd.58. The process of claim 54 further comprising coating one surface of said film   
     
     
        with a pressure sensitive adhesive. .Iaddend. .Iadd.59.  The process of claim 55 wherein said photoinitiator is selected from the group consisting of diacetoxyacetobenzophenone, benzophenone, 4-aminobenzophenone and 4'-methoxyacetophenone. .Iaddend. .Iadd.60. The process of claim 55 further comprising mixing said oligomer with at least one non-reactive thixotropic agent. .Iaddend. .Iadd.61. The process of claim 60 wherein said non-reactive thixotropic agent is selected from the group consisting of pyrogenic silica and bentonite clays. .Iaddend. .Iadd.62. A process in accordance with claim 54 wherein said vinyl terminated oligomer is dissolved in an organic solvent and the agent is admixed in said solvent solution. .Iaddend. .Iadd.63. A process in accordance with claim 62 wherein the vinyl terminated oligomer is co-dissolved with a polyurethane polymer which is the reaction product of: (d) dicyclohexyl methane diisocyanate;   (e) a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 daltons; and   (f) 1,4-butane diol. .Iaddend. .Iadd.64. The process of claim 63 wherein 80-99 parts by weight of said vinyl terminated oligomer are co-dissolved with 1-20 parts by weight of siad polyurethane polymer. .Iaddend. .Iadd.65. The process of claim 63 wherein said monomer is hydroxyethyl methacrylate and said macroglycol is a polypropylene glycol having a number average molecular weight of 500-3000 daltons. .Iaddend. .Iadd.66. The process of claim 63 further comprising providing a textile fabric and coating said textile fabric with said solvent solution to form said film. .Iaddend. .Iadd.67. The process of claim 66 wherein said textile fabric is first coated with a polyurethane polymer that is the reaction product of:   dicyclohexyl methane diisocyanate;   a polytetramethylene ether polyol having a number average molecular weight in the range of 1000-3000 daltons; and   1,4-butane diol   and then coated with said solvent solution. .Iaddend. .Iadd.68. A process in accordance with claim 54 wherein a sufficient amount of (c) is added so that only compounds with number average molecular weights of 1500-5000 are present. .Iaddend.