Compositions and medical devices utilizing bioabsorbable polymeric waxes and rapamycin

Abstract

The present invention is directed to medical devices and pharmaceutical or agricultural compositions, and seeds, each containing a synthetic, bioabsorbable, biocompatible polymeric wax that is the reaction product of a polybasic acid or derivative thereof, a polyol and a fatty acid, the polymeric wax having a melting point less than about 70° C., as determined by differential scanning calorimetry, and an effective amount of rapamycin or an analogue thereof.

1 . A medical device, comprising: an effective amount of rapamycin or an analogue thereof, and a synthetic, bioabsorbable, biocompatible polymeric wax comprising the reaction product of a polybasic acid or derivative thereof, a fatty acid; and a polyol, said polymeric wax having a melting point less than about 70° C., as determined by differential scanning calorimetry.  
   
   
       2 . The medical device of  claim 1  wherein said polymeric wax comprises the reaction product of said polybasic acid or derivative thereof and a monoglyceride, said monoglyceride comprising the reaction product of said fatty acid and said polyol.  
   
   
       3 . The medical device of  claim 2  wherein said polybasic acid or derivative thereof is selected from the group consisting of succinic acid, succinic anhydride, malic acid, tartaric acid, citric acid, diglycolic acid, diglycolic anhydride, glutaric acid, glutaric anhydride, adipic acid, pimelic acid, suberic acid, sebacic acid, fumaric acid, maleic acid, maleic anhydride, mixed anhydrides, esters, activated esters and acid halides.  
   
   
       4 . The medical device of  claim 2  wherein said monoglyceride is selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl glycerol, monolauroyl glycerol, monolinoleoyl glycerol and monooleoyl glycerol.  
   
   
       5 . The medical device of  claim 4  wherein said polybasic acid derivative is succinic anhydride.  
   
   
       6 . The medical device of  claim 1  wherein said polymeric wax has a number average molecular weight between about 1,000 g/mole and about 100,000 g/mole, as measured by gel permeation chromatography using polystyrene standards.  
   
   
       7 . The medical device of  claim 1  wherein said polymeric wax is branched.  
   
   
       8 . The medical device of  claim 1  wherein said polymeric wax comprises a copolymer.  
   
   
       9 . The medical device of  claim 9  wherein said wax copolymer comprises the reaction product of said polybasic acid or derivative thereof, a monoglyceride selected from the group consisting of monostearoyl glycerol, monopalmitoyl glycerol, monomyrisitoyl glycerol, monocaproyl glycerol, monodecanoyl glycerol, monolauroyl glycerol, monolinoleoyl glycerol and monooleoyl glycerol, and at least one additional polyol selected from the group consisting of ethylene glycol, 1,2-propylene glycol, 1,3-propanediol, bis-2-hydroxyethyl ether, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,8-octanediol, 1,10-decanediol, 1,12-dodecanediol, other diols, linear poly(ethylene glycol), branched poly(ethylene glycol), linear poly(propylene glycol), branched poly(propylene glycol), linear poly(ethylene-co-propylene glycol)s and branched poly(ethylene-co-propylene glycol)s.  
   
   
       10 . The medical device of  claim 1  further comprising an aliphatic polyester prepared from monomers selected from the group consisting of glycolide, L-lactide, D-lactide, meso-lactide, rac-lactide, ε-caprolactone, trimethylene carbonate, p-dioxanone, 1,4-dioxanone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and substituted derivatives thereof.  
   
   
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