Method for preventing restenosis using a substituted adenine derivative

Abstract

The present invention discloses a method for the prevention of atherosclerosis, its genesis, progression and restenosis in human patients undergoing treatments for arterial lesions such as PTA or atherectomy, and which may be accompanied by stent implantation. Further, the treatment method disclosed has applicability in all stages of atherosclerosis in which monocytes play a role. The compound utilized in the present method as the active agent is a 2-halo-2′-deoxyadenosine such as 2-chloro-deoxyadenosine (2-CdA). The treatment method of the present invention includes the administration of 14 doses of 2-CdA in the amount of 0.12 mg/kg. One dose is given intravenously before the coronary intervention, another is given intravenously after the intervention and the remaining twelve doses are given subcutaneously at weekly intervals over a subsequent three month period.

1. A method for preventing a restenosis at a location of an inflammation in the vasculature of a patient which comprises the steps of:
 apportioning a medicament into a plurality of therapeutically effective doses, wherein said medicament is selected from a group consisting of a substituted adenine derivative and a pharmacologically acceptable acid addition salt thereof, said medicament having the formula: 
                 
 
 
       wherein Y is a halogen, each said dose of said medicament being efficacious for responding to said inflammation by reducing monocytes in the blood to below a preselected level; and
 administering at least one of said doses to a human in accordance with a predetermined regimen.  
 
     
     
       2. The method as recited in  claim 1  wherein Y is chlonine  chlorine. 
     
     
       3. The method as recited in  claim 1  wherein said inflammation results from a catheter procedure. 
     
     
       4. The method as recited in  claim 3  wherein said catheter procedure is a percutaneous transluminal angioplasty (PTA) procedure. 
     
     
       5. The method as recited in  claim 3  wherein said catheter procedure is selected from a group consisting of an atherectomy procedure, a photolysis procedure and a radio frequency ablation procedure. 
     
     
       6. The method as recited in  claim 3  wherein said catheter procedure includes implantation of an arterial stent. 
     
     
       7. The method as recited in  claim 1  wherein said predetermined regime comprises the step of:
 preparing fourteen individual portions of said medicament;  
 administering a first said portion of said medicament to said human prior to a catheter procedure;  
 administering a second said portion of said medicament to said human subsequent said catheter procedure; and  
 administering one of said remaining twelve portions of said medicament at consecutive weekly intervals over a twelve week period immediately following said administering of said second said portion of said medicament.  
 
     
     
       8. The method as recited in  claim 7  wherein said first portion of said medicament is administered on the day of said catheter procedure and said second portion of said medicament is administered on the day immediately following said catheter procedure. 
     
     
       9. The method as recited in  claim 7  wherein each said portion of said medicament is approximately one twelve hundredths of a milligram per kilogram of body weight (0.12 mg/Kg). 
     
     
       10. The method as recited in  claim 7  wherein said first and second portions of said medicament are administered intravenously, and said remaining portions are administered subcutaneously. 
     
     
       11. A method for reducing the production of monocytes in a patient to prevent a restenosis wherein said method comprises the steps of:
 preparing fourteen individual portions of a medicament, wherein said medicament is selected from a group consisting of a substituted adenine derivative and a pharmacologically acceptable acid addition salt thereof, said medicament having the formula: 
                 
 
 
       wherein Y is a halogen;
 administering a first said portion of said medicament to said human prior to a catheter procedure;  
 providing a second said portion of said medicament to said human subsequent said catheter procedure; and  
 dispensing one of said remaining twelve portions of said medicament at consecutive weekly intervals over a twelve week period immediately following said administering of said second said portion of said medicament.  
 
     
     
       12. The method as recited in  claim 11  wherein said first portion of said medicament is administered on the day of said catheter procedure and said second portion of said medicament is administered on the day immediately following said catheter procedure. 
     
     
       13. The method as recited in  claim 11  wherein each said portion of said medicament is approximately one twelve hundredths of a milligram per kilogram of body weight (0.12 mg/Kg). 
     
     
       14. The method as recited in  claim 11  wherein said first and second portions of said medicament are administered intravenously, and said remaining portions are administered subcutaneously. 
     
     
       15. The method as recited in  claim 11  wherein Y is chlorine. 
     
     
       16. A method for preventing a restenosis at a location of an inflammation in the vasculature of a patient which comprises the steps of:
   apportioning a medicament into a plurality of therapeutically effective doses, wherein said medicament is selected from a group consisting of a substituted adenine derivative and a pharmacologically acceptable acid addition salt thereof, said medicament having the formula:                          wherein Y is a halogen, each said dose of said medicament being efficacious for responding to said inflammation by reducing monocytes in the blood to below a preselected level; and        administering at least one of said doses to a human topically with a carrier in accordance with a predetermined regimen.     
     
     
       17. The method as recited in  claim 16  wherein said carrier is a stent. 
     
     
       18. The method as recited in  claim 16  wherein Y is chlorine.