Methods and compositions for the prevention and treatment of atherosclerosis restenosis and related disorders
Methods and compositions for the prevention and treatment of all forms of atherosclerosis are described. Administration of compounds such as thalidomide, its analogs, hydrolysis products, metabolites, derivatives and precursors as well as additional compounds capable of inhibiting tumor necrosis factor α (TNF-α) are used in the invention. Also disclosed is the coating of prosthetic devices, such as stents, with the compounds of the invention for the prevention and/or treatment of restenosis.
1. A method of treating atherosclerosis in a mammal comprising administering to a mammal in need thereof an effective amount of a1-oxo-2-(2,6-dioxoperidin-3-yl)isoindoline sustituted with amino in the benzo ring.
2. A method of treating atherosclerosis in a mammal comprising administering to a mammal in need thereof an effective amount of 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline.
3. The method of claim 1 or 2 wherein the atherosclerosis is in the aorta, coronary artery, mesenteric arteries, or carotid arteries.
4. The method of claim 1 or 2 wherein the atherosclerosis is in a renal artery.
5. The method of claim 1 or 2 wherein the mammal is a human.
6. The method of claim 1 or 2 wherein approximately 0.01 mg/kg to 300 mg/kg of body weight is administered per day.
7. The method of claim 6 wherein approximately 0.1 mg/kg to 100 mg/kg of body weight is administered per day.
8. The method of claim 7 wherein approximately 0.5 mg/kg to 50 mg/kg of body weight is administered per day.
9. The method of claim 8 wherein approximately 1.0 mg/kg to 10 mg/kg of body weight is administered per day.
10. The method of claim 1 or 2 wherein the administration is oral.
11. A method of inhibiting restenosis in a mammal comprising administering to a mammal in need thereof an effective amount of 1-oxo 2-(2,6-dioxopiperidin-3-yl)isoindolines substituted with amino in the benzo ring.
12. A method of inhibiting restenosis in a mammal comprising administering to a mammal in need thereof an effective amount of 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline.
13. The method of claim 11 or 12 wherein approximately 0.01 mg/kg to 300 mg/kg of body weight administered per day.
14. The method of claim 13 wherein approximately 0.1 mg/kg to 100 mg/kg of body weight is administered per day.
15. The method of claim 14 wherein approximately 0.5 mg/kg to 50 mg/kg of body weight is administered per day.
16. The method of claim 15 wherein approximately 1.0 mg/kg to 10 mg/kg of body weight is administered per day.
17. The method of claim 11 or 12 wherein the treatment begins prior to surgical intervention.
18. The method of claim 17 wherein treatment begins prior to surgical intervention and is continued for about 4 to 12 weeks after the surgical intervention.
19. The method of claim 17 wherein the treatment begins about 12 hours or less prior to scheduled intervention.
20. The method of claim 18 wherein the treatment begins about 12 hours or less prior to scheduled intervention.
21. The method of claim 17 wherein the surgical intervention is percutaneous coronary intervention, percutaneous translurninal coronary angioplasty, carotid percutaneous transluminal angioplasty coronary by-pass grafting or coronary angioplasty with stent implantation.
22. The method of claim 17 wherein the surgical intervention is renal angioplasty, peripheral percutaneous transluminal intervention of the iliac, femoral or popliteal arteries or surgical intervention using impregnated artificial grafts.
23. The method of claim 11 or 12 wherein the surgical intervention is unscheduled and treatment begins at the time of surgery.
24. The method of claim 11 or 12 wherein the surgical intervention is unscheduled and treatment begins at the time of surgery and is discontinued about 4 to 12 weeks after the surgical intervention.
25. The method of claim 1 or 2 wherein the atherosclerosis is in the common iliac arteries, internal iliac arteries, external iliac arteries, or the pulmonary arteries.