Treatment and prevention of adhesions

Abstract

An inhibitor of adhesion formation which can be used to prevent adhesions within the abdominal cavity, particularly following surgical intervention, trauma or inflammation in the area is disclosed. Specifically, the most preferred compound of the present invention. Halofuginone, can be used to prevent collagen deposition from occurring within the peritoneum after surgical intervention, thereby inhibiting adhesion formation. Halofuginone, and related compounds, are useful in the prevention and treatment of both inflammatory and surgically induced adhesions, and in the treatment of congenital adhesions.

What is claimed is:  
     
       1. A method for the treatment of an adhesion in a subject, the adhesion forming a fibrous bridge between normally separated tissues, with the proviso that the adhesion is not a fibrous peritendinous adhesion, the method comprising the step of administering to the subject a pharmaceutically effective amount of a compound having a formula:                    
       wherein: 
       n is  1  or  2 ; 
       R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;  
       R 2  is a member of the group consisting of hydroxy, acetoxy and lower alkoxy, and  
       R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl, such that the fibrous bridge is treated.  
     
     
       2. The method of  claim 1 , wherein the adhesion is within an abdominal cavity. 
     
     
       3. The method of  claim 2 , wherein the adhesion arises from a cause selected from the group consisting of surgical intervention in said abdominal cavity, presence of a foreign body in said abdominal cavity, inflammation of a tissue in said abdominal cavity, trauma to said abdominal cavity, irradiation of said abdominal cavity, presence of a tumor in said abdominal cavity and administration of a drug capable of inducing an adhesion in the subject. 
     
     
       4. The method of  claim 3 , wherein said inflammation of said tissue is caused by microbial infection of said tissue. 
     
     
       5. The method of  claim 4 , wherein said inflammation is of a reproductive organ of a female subject. 
     
     
       6. The method of  claim 1 , wherein said compound is Halofuginone. 
     
     
       7. A method for substantially preventing formation of an adhesion in a subject, the adhesion forming a fibrous bridge between normally separated tissues, with the proviso that the adhesion is not a fibrous peritendinous adhesion, the method comprising the step of administering to the subject a pharmaceutically effective amount of a compound having a formula:                    
       wherein: 
       n is  1  or  2 ; 
       R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;  
       R 2  is a member of the group consisting of hydroxy, acetoxy and lower alkoxy, and  
       R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl, such that the formation of the fibrous bridge is prevented.  
     
     
       8. The method of  claim 7 , wherein the adhesion is within an abdominal cavity. 
     
     
       9. The method of  claim 8 , wherein the cause of the adhesion arises is selected from the group consisting of surgical intervention in said abdominal cavity, presence of a foreign body in said abdominal cavity, inflammation of a tissue in said abdominal cavity, trauma to said abdominal cavity, irradiation of said abdominal cavity, presence of a tumor in said abdominal cavity and administration of a drug capable of inducing an adhesion in the subject. 
     
     
       10. The method of  claim 9 , wherein said inflammation of said tissue is caused by microbial infection of said tissue. 
     
     
       11. The method of  claim 10 , wherein said inflammation is of a reproductive organ of a female subject. 
     
     
       12. The method of  claim 7 , wherein said compound is Halofuginone. 
     
     
       13. A method for inhibition of formation of an adhesion in a subject for treatment substantially before performance of a surgical procedure, the adhesion forming a fibrous bridge between normally separated tissues, with the proviso that the adhesion is not a fibrous peritendinous adhesion, the method comprising the step of administering to the subject a pharmaceutically effective amount of a compound having a formula:                    
       wherein: 
       n is  1  or  2 ; 
       R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;  
       R 2  is a member of the group consisting of hydroxy, acetoxy and lower alkoxy, and  
       R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl, such that the formation of the fibrous bridge is prevented.  
     
     
       14. The method of  claim 13 , wherein said compound is Halofuginone. 
     
     
       15. The method of  claim 14 , wherein the surgical procedure is performed in an abdominal cavity. 
     
     
       16. The method of  claim 15 , wherein the adhesion causes intestinal obstruction in the subject. 
     
     
       17. The method of  claim 15 , wherein the adhesion causes infertility in the subject. 
     
     
       18. A method for treatment of an inflammatory disease characterized by formation of an adhesion, the adhesion forming a fibrous bridge between normally separated tissues, with the proviso that the adhesion is not a fibrous peritendinous adhesion, the method comprising the step of administering to the subject a pharmaceutically effective amount of an antibiotic with a pharmaceutically effective amount of a compound having a formula:                    
       wherein 
       n is  1  or  2 ; 
       R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;  
       R 2  is a member of the group consisting of hydroxy, acetoxy and lower alkoxy, and  
       R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl, such that the fibrous bridge is treated.  
     
     
       19. The method of  claim 18 , wherein the inflammatory disease is pelvic inflammatory disease. 
     
     
       20. The method of  claim 18 , wherein said compound is Halofuginone.