Method and non-gelling composition for inhibiting post-surgical adhesions

Abstract

Non-gelling polyoxyalkylene compositions, and methods of their use for inhibiting surgical adhesion formation/reformation in mammals are disclosed. The useful non-gelling compositions preferably comprise polyoxyalkylene block copolymer at desired concentrations with or without a therapeutic agent. When used with an incorporated drug, the non-gelling compositions serve as a carrier providing sustained or prolonged release of the therapeutic agent.

What is claimed is:  
     
         1 . A method of delivering one or more drugs to a subject in need of treatment comprising administering a non-gelling aqueous composition comprising: 
 (1) about 70% to about 99% by weight of water;    (2) about 1% to about 30% by weight of a polyoxyalkylene block copolymer of the formula:    Y[(A) n -E-H] x   (I)    wherein A is a polyoxyalkylene moiety having an oxygen/carbon atom ratio of less than 0.5, x is at least 1, Y is derived from water or an organic compound containing x reactive hydrogen atoms, E is a polyoxyethylene moiety, n has a value such that the minimum molecular weight of A is between about 500 and about 900, as determined by the hydroxyl number of an intermediate of the formula:    Y[(A)-H] x   (II)    and the total average molecular weight of the polyoxyalkylene block copolymer is at least about 5000; and,    (3) a therapeutically effective amount of the drug.    
     
     
         2 . The method of  claim 1 , wherein Y is derived from a water soluble organic compound having 1 to about 6 carbon atoms.  
     
     
         3 . The method of  claim 1 , wherein said polyoxyalkylene block copolymer is selected from the group consisting of a polyoxyethylene-polyoxybutylene block copolymer, a polyoxyethylene-polyoxypropylene block copolymer and mixtures thereof, wherein the polyoxyethylene moiety constitutes at least about 70% by weight of the polyoxyalkylene block copolymer.  
     
     
         4 . The method of  claim 1 , wherein the pH of the aqueous composition is maintained at about 7.4±0.4.  
     
     
         5 . The method of  claim 1 , wherein said polyoxyalkylene block polymer is selected from block copolymers which form aqueous solutions at a concentration of about 1% to about 16% by weight of the total weight of said composition.  
     
     
         6 . The method of  claim 5 , wherein said polyoxyalkylene block polymer is selected from block copolymers which form aqueous solutions at a concentration of about 7% to about 14% by weight of the total weight of said composition.  
     
     
         7 . The method of  claim 6 , wherein Y is selected from the group consisting of propylene glycol, glycerin, pentaerythritol, trimethylolpropane, ethylenediamine, and mixtures thereof.  
     
     
         8 . The method of  claim 1 , wherein Y is derived from propylene glycol, A is a propylene oxide residue, and the intermediate of formula II has an average molecular weight of a least about 900.  
     
     
         9 . The method of  claim 1 , wherein Y is derived from butylene glycol, A is a butylene oxide residue, and the intermediate of formula II has an average molecular weight of at least about 500.  
     
     
         10 . The method of  claim 1 , wherein said polyoxyalkylene block copolymer is of the formula:  
       HO(C 2 H 4 O) b (C 4 H 8 O) a (C 2 H 4 O) b H  (III)  
       wherein a and b are integers such that the hydrophobe base represented by (C 4 H 8 O) has an average molecular weight of at least about 1000, as determined by hydroxyl number, and the polyoxyethylene chain constitutes at least about 60% by weight of the polyoxyalkylene block copolymer; or of the formula:  
       HO(C 2 H 4 O) b (C 3 H 6 O) a (C 2 H 4 O) b H  (IV)  
       wherein a and b are integers such the hydrophobe base represented by (C 3 H 6 O) has an average molecular weight of at least about 1500, as determined by hydroxyl number, the polyoxyalkylene chain constitutes at least about 60% by weight of the polyoxyalkylene block copolymer, and the block copolymer has a total average molecular weight of at least about 5,000; or of the formula:  
       [H(OC 2 H 4 ) b (OC 3 H 6 ) a ] 2 —N—CH 2 —CH 2 —N—[(C 3 H 6 O) a (C 2 H 4 O) b H] 2   (V)  
       wherein a and b are integers such that the polyoxyalkylene block copolymer has an average hydrophobe molecular weight of at least 2000, a hydrophile content of at least about 60%, and a total average molecular weight of at least about 5,000.  
     
     
         11 . The method of  claim 10 , wherein the total average molecular weight of the block copolymer is at least about 15,000.  
     
     
         12 . The method of  claim 10 , wherein the copolymer is:  
       H(OC 2 H 4 ) 101  (OCH(CH 3 )CH 2 ) 56 (OC 2 H 4 ) 101 OH.  
     
     
         13 . The method of  claim 1  wherein the composition is hyper-, iso-, or hypoosmotic to mammalian body tissues.