Method and composition for inhibiting cardiovascular cell proliferation

Abstract

Cardiovascular cell proliferation in a blood vessel subjected to trauma, such as angioplasty, vascular graft, anastomosis, or organ transplant, can be inhibited by contacting the vessel with a polymer consisting of from 6 to about 30 amino acid subunits, where at least 50% of the subunits are arginine, and the polymer contains at least six contiguous arginine subunits. Exemplary polymers for this purpose include arginine homopolymers 7 to 15 subunits in length.

1 - 28 . (canceled) 
     
     
         29 . A preservation solution comprising an arginine polymer and an isolated ex vivo blood vessel, graft, vein patch or organ, wherein the polymer is not conjugated to a biological agent. 
     
     
         30 . The preservation solution of  claim 29 , wherein the arginine polymer comprises between 6 and 30 contiguous arginine residues. 
     
     
         31 . The preservation solution of  claim 30 , wherein the arginine polymer comprises between 6 and 25 contiguous arginine residues. 
     
     
         32 . The preservation solution of  claim 31 , wherein the arginine polymer comprises between 6 and 10 contiguous L-arginine residues. 
     
     
         33 . The preservation solution of  claim 29 , wherein the arginine polymer comprises between 7 and 15 contiguous L-arginine residues. 
     
     
         34 . The preservation solution of  claim 29 , wherein the arginine polymer is an arginine homopolymer. 
     
     
         35 . The preservation solution of  claim 34 , wherein the arginine homopolymer comprises 6 to 25 arginine residues. 
     
     
         36 . The preservation solution of  claim 35 , wherein the arginine homopolymer comprises 6 to 15 arginine residues. 
     
     
         37 . The preservation solution of  claim 34 , wherein the arginine homopolymer comprises 7 to 10 arginine residues. 
     
     
         38 . The preservation solution of  claim 29 , wherein the concentration of the arginine polymer is between 0.01 μM and 100 μM. 
     
     
         39 . The preservation solution of  claim 38 , wherein the concentration of the arginine polymer is between 1 μM and 50 μM. 
     
     
         40 . The preservation solution of  claim 39 , wherein the concentration of the arginine polymer is between 1 μM and 25 μM. 
     
     
         41 . A composition comprising:
 an amino acid polyarginine polymer comprising at least 6 contiguous arginine residues and comprising between 7- and 10 arginine residues, wherein the polymer is not conjugated to a biological agent;   an isolated ex vivo blood vessel, graft, vein patch or organ; and,   a pharmaceutically acceptable excipient, carrier, vehicle, salt, buffer, preservative or cardioplegic agent.   
     
     
         42 . A composition comprising:
 an amino acid polyarginine polymer, an isolated ex vivo blood vessel, graft, vein patch or organ, and   a pharmaceutically acceptable excipient, carrier, vehicle, salt, buffer, preservative or cardioplegic agent,   
       wherein the polymer is present in the composition at a concentration of between 0.01 μM and 100 μM and wherein the polymer is not conjugated to a biological agent. 
     
     
         43 . A composition comprising:
 an amino acid polyarginine polymer, wherein the polymer is not conjugated to a biological agent; and,   a pharmaceutically acceptable excipient, carrier, vehicle, salt, buffer, preservative or cardioplegic agent,   
       wherein the composition further comprises an isolated ex vivo blood vessel, graft, vein patch or organ. 
     
     
         44 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer comprises between 6 and 30 amino acids. 
     
     
         45 . The composition of  claim 42  or  43 , wherein the polymer comprises at least 6 contiguous arginine subunits. 
     
     
         46 . The composition of  claim 42  or  43 , wherein the polymer comprises 7-10 arginine residues. 
     
     
         47 . The composition of  claim 42  or  43 , wherein the polymer comprises 6-15 arginine residues. 
     
     
         48 . The composition of  claim 42  or  43 , wherein the polymer comprises 6-25 arginine residues. 
     
     
         49 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer comprises at least 50% arginine subunits. 
     
     
         50 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer comprises at least 70% arginine subunits. 
     
     
         51 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer comprises at least 90% arginine subunits. 
     
     
         52 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer is an arginine homopolymer. 
     
     
         53 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer is present in the composition at a concentration of between 1 μM and 50 μM. 
     
     
         54 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer is present in the composition at a concentration of between 1 μM and 25 μM. 
     
     
         55 . The composition of  claim 41 ,  42 , or  43 , wherein non-arginine subunits of the polymer do not reduce the rate of membrane transport of the polymer. 
     
     
         56 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer is uncapped. 
     
     
         57 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer is capped. 
     
     
         58 . The composition of  claim 41 ,  42 , or  43 , wherein the polymer is present at a concentration that reduces the level of intimal hyperplasia when contacted to a blood vessel. 
     
     
         59 . The composition of  claim 41 ,  42 , or  43 , wherein the composition is present in a delivery device. 
     
     
         60 . The composition of  claim 41 ,  42 , or  43 , wherein said polyarginine polymer comprises a concentration of 0.1 μM, 1 μM, 10 μM, 50 μM, or between 0.01 and 100 μM.