Treatment of restenosis using temsirolimus

Abstract

Described herein are methods for distributing temsirolimus to a tissue surrounding a blood vessel for treating vascular diseases. Also disclosed are injectable compositions of temsirolimus for delivery into the tissue surrounding a blood vessel for treating vascular diseases.

What is claimed is: 
     
         1 . An injectable composition comprising temsirolimus or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient for use in treating restenosis in a peripheral artery of a human subject, wherein the composition is suitable for adventitial delivery to the peripheral artery, wherein the composition is suitable for direct injection to a vascular disease site in a tissue surrounding a wall of the peripheral artery or in the wall of the peripheral artery via a laterally extending needle from a catheter advanced through vasculature of the human subject in a therapeutically effective amount effective to cause patency at the disease site after administration to increase or minimally decrease when compared to patency at the disease site at the time of administration. 
     
     
         2 . The injectable composition for use of  claim 1 , wherein the composition is suitable for adventitial delivery in the leg. 
     
     
         3 . The injectable composition for use of  claim 2 , wherein the composition is suitable for adventitial delivery below the knee. 
     
     
         4 . The injectable composition for use of  claim 2 , wherein the composition is suitable for adventitial delivery in the leg above the knee. 
     
     
         5 . The injectable composition for use of  claim 2 , wherein the composition is suitable for adventitial delivery to a below-knee popliteal or tibial vessel. 
     
     
         6 . The injectable composition of  claim 1 , wherein the therapeutically effective amount of temsirolimus is about 1 μg to 50 mg. 
     
     
         7 . The injectable composition of  claim 6 , wherein the therapeutically effective amount of temsirolimus is about 10 μg to 20 mg. 
     
     
         8 . The injectable composition of  claim 7 , wherein the therapeutically effective amount of temsirolimus is about 25 μg to 10 mg. 
     
     
         9 . The injectable composition of  claim 1 , wherein an injection volume of the composition is about 0.01 ml to about 50 ml. 
     
     
         10 . The injectable composition of  claim 9 , wherein the injection volume of the composition is about 0.5 ml to about 20 ml. 
     
     
         11 . The injectable composition of  claim 1 , wherein the therapeutically effective amount of temsirolimus is about 0.005 mg to 5 mg per cm of longitudinal length of the disease site in the blood vessel. 
     
     
         12 . The injectable composition of  claim 11 , wherein the therapeutically effective amount of temsirolimus is about 0.025 mg to 1 mg per cm of longitudinal length of the disease site in the blood vessel. 
     
     
         13 . The injectable composition of  claim 1 , wherein a concentration of temsirolimus is about 0.01 mg/mL to about 2.0 mg/mL. 
     
     
         14 . The injectable composition of  claim 13 , wherein the concentration of temsirolimus is about 0.1 mg/mL to about 0.5 mg/mL. 
     
     
         15 . The injectable composition of  claim 14 , wherein the concentration of temsirolimus is about 0.1 mg/mL to about 0.4 mg/mL. 
     
     
         16 . The injectable composition for use of  claim 1 , wherein the pharmaceutically acceptable excipient is 0.9% sodium chloride injection USP, dehydrated alcohol, dl-alpha tocopherol, anhydrous citric acid, polysorbate 80, polyethylene glycol 400, propylene glycol, or a combination thereof. 
     
     
         17 . The injectable composition of  claim 1 , wherein the tissue comprises an adventitia tissue around the peripheral artery. 
     
     
         18 . The injectable composition of  claim 1 , wherein the tissue comprises the perivascular tissue around the peripheral artery. 
     
     
         19 . The injectable composition of  claim 1 , wherein the vascular disease site comprises the site of tissue damage or sites within 100 mm of the tissue damage. 
     
     
         20 . The injectable composition of  claim 1 , wherein a cross-sectional area at the disease site decreased no more than 60% when compared to cross-sectional area at the disease site at the time of administration.