Polyetherurethane urea polymers as space filling tissue adhesives

Claim 1

A space filling tissue adhesive which comprises a polyetherurethane urea polymer formed by reaction of a purified diisocyanate polyetherurethane prepolymer with an aqueous solution comprising, for each mol of diisocyanate prepolymer, substantially one mol of a chain extending compound of the formula ##STR4## wherein n is zero or an integer from 1-8; X is --OH, --NHC(NH)NH 2 or --NHR; Y is hydrogen or --COOH; R is hydrogen or (C 1 -C 3 )alkyl; R 1 is hydrogen or (C 1 -C 3 )alkyl; and R 2 and R 3 are taken separately, and R 2 is hydrogen or (C 1 -C 3 )alkyl; and R 3 is hydrogen or (C 1 -C 3 )alkyl; or R 2 and R 3 are taken together and are --CH 2 --, with the proviso that when R 2 and R 3 are so taken, n is 1, 2 or 3; or a pharmaceutically acceptable cationic or acid addition salt thereof; said purified prepolymer having been previously formed by reacting di(4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocyclohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000; and comprised predominantly of individual molecules consisting of said reactants in 2:1 molar ratio, respectively.

Claim 17

A method surgical repair of a skull cavity or a dural incision, in a human or animal, which comprises the steps of: (a) producing a viscous polymerizing liquid by reacting a purified diisocyanate polyetherurethane prepolymer with an aqueous solution comprising, for each mol of diisocyanate prepolymer, substantially one mol of a chain extending compound of the formula ##STR5## wherein n is zero or an integer from 1-8; X is --OH, --NHC(NH)NH 2 or --NHR; Y is hydrogen or --COOH; R is hydrogen or (C 1 -C 3 )alkyl; R 1 is hydrogen or (C 1 -C 3 )alkyl; and R 2 and R 3 are taken separately; and R 2 is hydrogen or (C 1 -C 3 )alkyl; and R 3 is hydrogen or (C 1 -C 3 )alkyl; or R 2 and R 3 are taken together and are --CH 2 --, with the proviso that when R 2 and R 3 are so taken, n is 1, 2 or 3; or a pharmaceutically acceptable cationic or acid addition salt thereof; said purified prepolymer having been previously formed by reacting di(4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocy clohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000; and comprised predominantly of individual molecules consisting of said reactants in 2:1 molar ratio, respectively; (b) while still in liquid form, filling said cavity or covering said dural incision with said viscous liquid to form an adhesive graft; and (c) allowing said adhesive graft to solidify and adhere to adjoining tissue in place.

Claim 18

A method surgical repair of a skull cavity or a dural incision, in a human or animal, which comprises the steps of: (a) producing a viscous polymerizing liquid by reacting a purified diisocyanate polyetherurethane prepolymer with an aqueous solution comprising, for each mol of diisocyanate prepolymer, substantially one mol of a chain extending compound of the formula ##STR5## wherein n is zero or an integer from 1-8; X is --OH, --NHC(NH)NH 2 or --NHR; Y is hydrogen or --COOH; R is hydrogen or (C 1 -C 3 )alkyl; R 1 is hydrogen or (C 1 -C 3 )alkyl; and R 2 and R 3 are taken separately; and R 2 is hydrogen or (C 1 -C 3 )alkyl; and R 3 is hydrogen or (C 1 -C 3 )alkyl; or R 2 and R 3 are taken together and are --CH 2 --, with the proviso that when R 2 and R 3 are so taken, n is 1, 2 or 3; or a pharmaceutically acceptable cationic or acid addition salt thereof; said purified prepolymer having been previously formed by reacting di(4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocy clohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000; and comprised predominantly of individual molecules consisting of said reactants in 2:1 molar ratio, respectively; (b) while still in liquid form, filling said cavity or covering said dural incision with said viscous liquid to form an adhesive graft; and (c) allowing said adhesive graft to solidify and adhere to adjoining tissue in place.

Claim 52

A method of purifying a crude diisocyanate polyurethane prepolymer formed by reacting di( 4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocyclohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000; comprised of unreacted diisocyanato compound and prepolymer, the latter comprised predominantly of individual molecules consisting of said reactants in 2:1 molar ratio, respectively, which comprises the steps of: (a) dissolving the crude prepolymer in acetonitrile containing up to 25% toluene by volume; (b) removing said unreacted diisocyanato compound by continuously extracting the resulting solution with petroleum ether having a boiling point range in the range of 30°-60° C.; and (c) recovering said prepolymer in purified form.

Claim 53

A method of purifying a crude diisocyanate polyurethane prepolymer formed by reacting di( 4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocyclohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000; comprised of unreacted diisocyanato compound and prepolymer, the latter comprised predominantly of individual molecules consisting of said reactants in 2:1 molar ratio, respectively, which comprises the steps of: (a) dissolving the crude prepolymer in acetonitrile containing up to 25% toluene by volume; (b) removing said unreacted diisocyanato compound by continuously extracting the resulting solution with petroleum ether having a boiling point range in the range of 30°-60° C.; and (c) recovering said prepolymer in purified form.

Claim 64

A method of preparing a diisocyanate polyurethane prepolymer which comprises reacting a 2-4 molar excess of di(4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocyclohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000, at 15°-30° C. in a non-polar aprotic solvent until reaction is substantially complete, said prepolymer comprised predominantly of individual molecules consisting of the diisocyanate and polyetherglycol reactants in 2:1 molar ratio, respectively.

Claim 65

A method of preparing a diisocyanate polyurethane prepolymer which comprises reacting a 2-4 molar excess of di(4-isocyanatophenyl)methane, di(4-isocyanatocyclohexyl)methane, 1,4-diisocyanatocyclohexane, 4-(4-isocyanatocyclohexyl)cyclohexyl isocyanate, di(4-isocyanatophenyl)ether or di(4-isocyanatocyclohexyl)ether with a polypropyleneglycol or polytetramethyleneglycol of average molecular weight in the range of about 650-5000, at 15°-30° C. in a non-polar aprotic solvent until reaction is substantially complete, said prepolymer comprised predominantly of individual molecules consisting of the diisocyanate and polyetherglycol reactants in 2:1 molar ratio, respectively.