Amino acid derivatives and absorbable polymers therefrom

Abstract

The present invention relates to the discovery of new class of hydrolysable amino acid derivatives and absorbable polyester amides, polyamides, polyepoxides, polyureas and polyurethanes prepared therefrom. The resultant absorbable polymers are useful for drug delivery, tissue engineering, tissue adhesives, adhesion prevention, bone wax formulations, medical device coatings, stents, stent coatings, highly porous foams, reticulated foams, wound care, cardiovascular applications, orthopedic devices, surface modifying agents and other implantable medical devices. In addition, these absorbable polymers should have a controlled degradation profile.

1 - 18 . (canceled) 
     
     
         19 . A medical or surgical article, comprising a polymer formed from a monomer of formula N or V: 
       
         
           
           
               
               
           
         
         wherein: 
         R″ is selected from: alkyl, aryl, and arylalkyl-, wherein:
 (a) the alkyl moiety has from 1-36 carbon atoms; 
 (b) one or more —CH 2 — groups of the alkyl moiety are replaced by —O—, —S—, or an ester group, wherein the ester group is selected from low molecular weight polyesters and polyethers; and, 
 (c) the alkyl and aryl groups are optionally substituted with one or more lower alkyl groups; 
 
         alternatively, R″ is a biologically active substance 
         wherein the medical or surgical article is selected from: drug delivery systems, tissue adhesives, tissue engineering, bone wax formulations, stent coatings, stents, porous devices, implantable medical devices, molded articles, wound closure devices, coatings, fibers or filaments, ligatures, needles, films, knitted products, foodstuffs, nutritional supplements, nutriceuticals, cosmetics, pharmaceuticals, biodegradable chewing gums, flavors, controlled drug delivery systems, solvents for drugs, foams, orthopedic devices, surface modifying agents, wound and/or burn dressings or coverings, and degradable containers and packaging materials. 
       
     
     
         20 . The medical or surgical article of  claim 19 , wherein alkyl is selected from isopentyl and neopentyl. 
     
     
         21 . The medical or surgical article of  claim 19 , wherein the compound is of formula N. 
     
     
         22 . The medical or surgical article of  claim 21 , wherein R″ is a biologically active substance selected from: Capsaicin, Triclosan, Chloroxylenol, Clioquinol, Nitroxoline, Oxyquinoline, Paracetamol, Tioxolone, Diflunisal, Naproxen, Diclofenac, Vitamin E, Butylated hydroxytoluene, and Butylated hydroxylanisol. 
     
     
         23 . The medical or surgical article of  claim 21 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         24 . The medical or surgical article of  claim 19 , wherein the compound is of formula V. 
     
     
         25 . The medical or surgical article of  claim 24 , wherein R″ is a biologically active substance selected from: Capsaicin, Triclosan, Chloroxylenol, Clioquinol, Nitroxoline, Oxyquinoline, Paracetamol, Tioxolone, Diflunisal, Naproxen, Diclofenac, Vitamin E, Butylated hydroxytoluene, and Butylated hydroxylanisol. 
     
     
         26 . The medical or surgical article of  claim 24 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         27 . The medical or surgical article of  claim 19 , wherein the surgical article is a tissue adhesive. 
     
     
         28 . The medical or surgical article of  claim 19 , wherein the surgical article is a stent coating. 
     
     
         29 . The medical or surgical article of  claim 19 , wherein the surgical article is a stent. 
     
     
         30 . The medical or surgical article of  claim 19 , wherein the surgical article is an implantable medical device selected from: stents, drug delivery devices or systems, prosthetic devices, rods pins, tubes, clamps, screws, plates, clips, films, meshes, staples, hooks, buttons, snaps, bone substitutes, intrauterine devices, anastomosis rings, surgical dressings, draining or testing tubes or capillaries, surgical instruments, vertebral discs, extracorporeal tubing for kidney and heart-lung machines, artificial skin. 
     
     
         31 . The medical or surgical article of  claim 30 , wherein the controlled drug delivery system is selected from: self-supporting films, hollow tubes, beads, and gels. 
     
     
         32 . The medical or surgical article of  claim 19 , wherein the controlled drug delivery system, further comprises: one or more biologically or pharmacologically active agents physically embedded or dispersed in the controlled drug delivery system. 
     
     
         33 . The medical or surgical article of  claim 19 , wherein the surgical article is a foam. 
     
     
         34 . The medical or surgical article of  claim 33 , wherein the foam is selected from: highly porous foams and reticulated foams. 
     
     
         35 . The medical or surgical article of  claim 19 , wherein the surgical article is a knitted product selected from: woven or non-woven products including: textile structures, burn dressings, hernia patches, medicated dressings, fascial substitutes, gauze, fabric, sheet, felt, sponge for liver hemostasis, gauze bandages, arterial graft or substitutes, and bandages for skin surfaces. 
     
     
         36 . The medical or surgical article of  claim 19 , wherein the polymer is further polymerized with a lactone monomer selected from: glycolide, lactide, ε-caprolactone, trimethylene carbonate, δ-valerolactone, β-butyrolactone, morpholinedione, pivalolactone, ε-decalactone, 2,5-diketomorpholine, p-dioxanone, or a combination thereof. 
     
     
         37 . The medical or surgical article of  claim 19 , further comprising: filler. 
     
     
         38 . The medical or surgical article of  claim 37 , wherein the filler is selected from the group consisting of: hydroxyapatite, tricalcium phosphate, and bioglass.