Covalently grafted pharmaceutically active polymers
The invention relates to graftable polymers comprising biologically active agents and the use of such polymers in the manufacture of shaped articles, such as implantable medical devices and catheters. The graftable polymers are covalently grafted to a surface via one or more grafting moieties incorporated into the pharmaceutically-active graftable polymer. The coated articles of the invention can further comprise tie-coats, and the ratio of polymer:tie coat can be used to adjust the rate of drug elution.
1. A graftable polymer having the following structure:
wherein
(i) each Bio is, independently, one or more biologically active agents or precursors thereof;
(ii) C1 is a coupling segment
(iii) C2 is a hydrolysable coupling segment or a polyamide linker susceptible to hydrolysis by a peptidase enzyme linking Bio to Bio;
(iv) Oligo comprises a repeating monomeric unit or units that number less than 50 monomeric units and has a molecular weight less than 5 KDa;
(v) G″ is a grafting moiety that has the following structure:
wherein, independently,
a. X is either —NH— or —O—;
b. m is an integer between 1 and 6;
c. n is an integer between 0 and 6; and
d. R is an optional substituent selected from —H; —NO 2 , or —CF 3 ;
wherein each of n, o, and p is independently an integer greater than 0, and
wherein G″ is covalently tethered to Bio, C1, C2, or Oligo.
2. The graftable polymer of claim 1 , wherein Bio comprises ciprofloxacin and/or chlorhexidine.
3. The graftable polymer of claim 1 , wherein G″ is
4. The graftable polymer of claim 3 , wherein
Bio is ciprofloxacin or chlorhexidine;
C1 comprises 2,2,4-trimethylhexamethylene diisocyanate (THDI);
Oligo comprises poly(ε-caprolactone) diol (PCL); and
5. The graftable polymer of claim 1 , wherein said graftable moiety requires photolytic or thermolytic activation for grafting to a polymer surface.