Gamma-tocopherol therapy for restenosis prevention

Abstract

A stent is provided in combination with delivery of a tocopherol agent, and in particular a des-methyl tocopherol agent, and further beneficially a gamma-tocopherol agent, so as to reduce restenosis along the vessel or other lumenal wall where the stent is implanted. In particular applications, the stent is an endolumenal stent, and more specific beneficial applications is an endovascular stent, and the gamma-tocopherol elutes from a coating or carrier coupled with the stent. Certain combinations are provided with the des-methyl-tocopherol or phytyl substituted chromanol, e.g. gamma-tocopherol, combined with an additional agent such as an anti-restenosis agent, e.g. sirolimus, tacrolimus, everolimus, or paclitaxel, in order to provide synergistic benefit to tissues along the stented or recanalized regions. Other forms of tocopherol or tocotrienol, or other phytyl substituted chromanols, and other compounds such as palm oil, are ailso contemplated. for use to treat restenosis.

1 - 44 . (canceled) 
     
     
         45 . A method for stimulating or promoting vascular wound healing of an endovascular wall injury caused during a vascular interventional procedure, comprising:
 delivering a pharmaceutically acceptable preparation of a bioactive agent comprising a tocopherol agent to the site of endovascular wall injury.   
     
     
         46 . The method of  claim 45 , wherein said vascular wound healing is induced or promoted by locally delivering said tocopherol agent to said site of endovascular wall injury. 
     
     
         47 . The method of  claim 45 , wherein said tocopherol agent comprises at least one agent selected from the group consisting of a des-methyl-tocopherol agent, a phytyl substituted chromanol agent and a gamma-tocopherol agent, or a precursor, analog, or derivative thereof. 
     
     
         48 . The method of  claim 47 , wherein said tocopherol agent comprises gamma-tocopherol. 
     
     
         49 . The method of  claim 45  wherein said tocopherol agent comprises a DNA plasmid encoding the production of said tocopherol agent, or a precursor, analog or derivative thereof. 
     
     
         50 . The method of  claim 45  wherein said tocopherol agent comprises a viral or non-viral gene vector encoding the production of said tocopherol agent. 
     
     
         51 . The method of  claim 45  wherein said tocopherol agent is delivered to said site of endovascular wall injury by a vascular stent that holds and releases the tocopherol agent at said site of endovascular wall injury. 
     
     
         52 . The method of  claim 51 , wherein said vascular stent is coated or adsorbed with a delivery carrier containing the tocopherol agent. 
     
     
         53 . The method of  claim 51 , wherein said vascular stent is adapted to elute the bioactive agent. 
     
     
         54 . The method of  claim 45 , wherein said tocopherol agent is delivered to said site of endovascular wall injury by an angioplasty balloon. 
     
     
         55 . A method for reducing restenosis in response to an endolumenal wall injury, comprising:
 implanting an endolumenal stent at a site of an endovascular wall injury; and   administering a therapeutic dose of a tocopherol agent that comprises at least one agent selected from the group consisting of des-methyl tocopherol agent, a phytyl substituted chromanol agent and gamma tocopherol or a palm oil agent, in a manner providing a higher bioactivity of the tocopherol agent at said site of endovascular wall injury than elsewhere in the body and sufficient to reduce restenosis at said site following stent implantation.   
     
     
         56 . The method of  claim 55  wherein said tocopherol agent is gamma tocopherol. 
     
     
         57 . The method of  claim 55 , further comprising:
 administering in combination with said tocopherol agent, a dose of an antirestenosis agent in a manner that provides a higher bioactivity of said anti-restenosis agent at said site of endovascular wall injury than elsewhere in the body and sufficient to inhibit restenosis at said site following stent implantation.   
     
     
         58 . The method of  claim 57 , wherein said anti-restenosis agent comprises at least one agent selected from the group consisting of sirolimus, tacrolimus, everolimus, ABT-578, paclitaxel, dexamethasone, 17-beta-estradiol, steroid, des-aspartate angiotensin I (DAA-1), angiotensin converting enzyme inhibitor (ACE inhibitor), angiotensin II receptor blocker, tachykinin, sialokinin, apocynin, pleiotrophin, exochelin, an iron chelator, VEGF, heparin, coumadin, clopidogrel, Iib/IIia inhibitor, nitric oxide, a nitric oxide donor, an eNOS antagonist, a nitric oxide synthesis promoter, and a statin, or a precursor, analog, or derivative thereof, or a combination or blend thereof. 
     
     
         59 . The method of  claim 57 , wherein one of said tocopherol agent and said anti-restenosis agent is eluted from the implanted stent, and wherein the other of said tocopherol agent and the anti-restenosis agent is delivered systemically. 
     
     
         60 . The method of  claim 57 , wherein at least one of said tocopherol agent and said anti-restenosis agent is delivered locally to the location. 
     
     
         61 . The method of  claim 57 , wherein both of said tocopherol agent and said anti-restenosis agent is eluted from the implanted stent.