Devices and compounds for treating arterial restenosis

Abstract

Described herein is the use of ADPRT decoy substrates to treat or prevent proliferative disorders. In one example, MIBG is shown to prevent restenosis in damaged vessels. In one embodiment, MIBG is combined with an adhesive agent for localizing the mixture to the site of injury. As a result of this arrangement, MIBG is not systemically released.

1 . A device for use in treatment of vascular stenosis, comprising: 
 a stent body and an ADPRT decoy substrate on or in the stent body.    
     
     
         2 . The device according to  claim 1  further comprising an adhesive agent  
     
     
         3 . The device according to  claim 2 , wherein said adhesive agent is biodegradable.  
     
     
         4 . The device according to  claim 3 , wherein said adhesive agent is fibrin glue.  
     
     
         5 . The device according to  claim 1 , wherein the ADPRT decoy substrate is selected from the group consisting of MIBG, NBAG, MGAG, NAP and NBGH.  
     
     
         6 . The device according to  claim 5  wherein the ADPRT decoy substrate is MIBG.  
     
     
         7 . A pharmaceutical composition comprising an ADPRT decoy substrate; and an adhesive.  
     
     
         8 . The pharmaceutical composition of  claim 7 , further comprising a suitable excipient.  
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the ADPRT decoy substrate is selected from the group consisting of MIBG, NBAG, MGAG, NAP and NBGH.  
     
     
         10 . The pharmaceutical composition of  claim 9  wherein the ADPRT decoy substrate is MIBG.  
     
     
         11 . The pharmaceutical composition of  claim 7 , wherein said adhesive agent is biodegradable.  
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein said adhesive agent is fibrin glue.  
     
     
         13 . A method for ameliorating at least one symptom of vascular stenosis, comprising: 
 performing angioplasty at a site of vascular stenosis; and    implanting a vascular stent at the site of said angioplasty, said stent comprising an effective amount of an ADPRT decoy substrate,    thereby ameliorating at least one symptom of vascular stenosis.    
     
     
         14 . The method of  claim 13 , wherein said ADPRT decoy substrate is selected from the group consisting of: MIBG, NBAG, GBG, MGAG, MBAG, CF3GBG, PhGBG, dodine, GAA, GPA, GBA, creatine synthalin A, synthaline B, alkylguanylhydrazones, aminoguanylhydrazones, acetylguanylhydrazones, arylguanylhydrazones, haloarylguanylhydrazones, bis(guanylhydrazones), tris(guanylhydrazones), and hirudonine.  
     
     
         15 . The method of  claim 14 , wherein said ADPRT decoy substrate is selected from the group consisting of MIBG, NBAG, MGAG, NAP and NBGH.  
     
     
         16 . The method of  claim 15 , wherein said ADPRT decoy substrate is MIBG.  
     
     
         17 . A kit comprising an ADPRT decoy substrate for treating or preventing an injury-related disorder and instructions for administration of said ADPRT decoy substrate for the treatment of an injury-related disorder.  
     
     
         18 . A method of inhibiting restenosis comprising: 
 applying an effective amount of a pharmaceutical composition comprising an ADPRT decoy substrate and a pharmaceutically acceptable excipient to a damaged vessel, said ADPRT decoy substrate selected from the group consisting of: MIBG, NBAG, GBG, MGAG, MBAG, CF3GBG, PhGBG, dodine, GAA, GPA, GBA, creatine, synthalin A, synthaline B, alkylguanylhydrazones, aminoguanylhydrazones, acetylguanylhydrazones, arylguanylhydrazones, haloarylguanylhydrazones, bis(guanylhydrazones), tris(guanylhydrazones), and hirudonine.    
     
     
         19 . The method according to  claim 18 , wherein said composition comprises a combination of at least two ADPRT decoy substrates.  
     
     
         20 . The method according to  claim 18 , wherein said composition further comprises an adhesive agent.  
     
     
         21 . The method according to  claim 18 , wherein said composition is coated on a vascular stent.  
     
     
         22 . A method of inhibiting restenosis comprising: 
 applying an effective amount of a pharmaceutical composition comprising an ADPRT decoy substrate and an pharmaceutically acceptable excipient to a damaged vessel, said ADPRT decoy substrate having the general structure:                          R2    wherein    R, R1 and R2 are independently selected from the group consisting of: H, CH3, CH2CH3, CH2(CH2)1-16CH3, C(CH3)3, CH2C(CH3)3, CH2C(CH3)3, CH(CH3)CH2CH2CH3, CH2CH(CH3)CH2CH2CH3, CH2CH(CH3)CH2CH2CH(CH3)2, C(CH3)2CH2C(CH3)3, CH2CH2CH(CH3)CH2C(CH3)3, 5, 6 and 8 member carbon rings, substituted benzene rings, substituted benzyl rings, CH2CH2SH, CH2CH2CH2SH, CH2CH2SCH3, CH2CH2SCH2CH3, CH2COOH, CH2CH2COOH, CH(CH3)COOH, CH2(CH2)2COOH, CH2(CH2)9COOH, CH(COOH)CH2(C6H5), OCH2COOH, CH(COOH)CH2COOH, COOCH2CH3, CH2CH2OCO(C6H5), CSNH2, CH2(CH2)3OCONHCH3, CH2(CH2)2OCONH2, CH2(CH2)2NHCOCF3, NHCOCH(Cl)2, CONH2, CH(COOC2H5)CH2OH, CH(CH3)CH2COOCH2CH3,NH2, NH(CH3), OH, OCH3, O(CH2)2OH, O(CH2)3OH, OC6H5, O(CH2)3C6H5, CH2CH2OH, CH2CH(OH)C6H5, CH2(CH2)2OH, CH2(CH2)3OH, CH2(CH2)5OH, CH2CH2NH2, thiadiaxoles, COR (wherein R is , for example, H, CH3, C6H5, (CH2)1-9CH3 or a substituted benzene ring), pyridine or substituted pyridine, napthalene, substituted naphthalene, sulfonic acid, heterocyclic compounds, substituted phenyl, and phenyl, said substituents being selected from the group consisting of Cl, Br, I, F, COOH, CN, CF3, SH, SCH2CH2, NO2, H, CH3, NH2 and SCH(CH3)2.    
     
     
         23 . The method according to  claim 22 , wherein said composition comprises a combination of at least two ADPRT decoy substrates.  
     
     
         24 . The method according to  claim 22 , wherein said composition further comprises an adhesive agent.  
     
     
         25 . The method according to  claim 22 , wherein said composition is coated on a vascular, stent