Surgical Mesh for Controlled Release of a Bioactive Agent

Abstract

Suture-specific coatings having a number average molecular weight not exceeding 20 kDa, a melting temperature above 37° C., and heat of fusion exceeding 20 J/g, are formed of copolyesters of polycaprolactone or of ε-caprolactone and at least one cyclic monomer forming a segmented polyester chain initiated by a polyaxial crystalline organic compound or an amorphous polyaxial polymeric initiator and include from about 0.01 to about 10 weight percent of at least one molecularly dispersed bioactive agent.

What is claimed is: 
     
         1 . A polymeric drug carrier, suture-specific coating for a suture, comprising:
 a crystalline, polyaxial copolyester, absorbable in at least one organic solvent, the copolyester selected from the group consisting of a copolyester of polycaprolactone and a copolyester of ε-caprolactone and at least one cyclic monomer selected from the group consisting of lactide, glycolide and trimethylene carbonate, the copolyester having a weight average molecular weight of up to about 20 kDa, a melting temperature (T m ) of greater than about 37° C., and a heat of fusion (ΔH f ) of greater than about 20 J/g,   the copolyester having molecularly dispersed therein from about 0.01 to about 15 weight percent of at least one bioactive agent selected from antimicrobial agents, antiviral agents, antineoplastic agents, anti-inflammatory agents, pain-relieving agents, anesthetic agents and tissue-regenerative agents,   wherein the coating may be applied to monofilament sutures at a level efficacious for the controlled release of the at least one bioactive agent for a period of greater than about three days and the coating may be applied to braided multifilament sutures at a level efficacious for the controlled release of the at least one bioactive agent for a period of greater than about two weeks.   
     
     
         2 . A polymeric drug carrier, suture-specific coating as set forth in  claim 1  wherein the copolyester is made by end-grafting an amorphous, monocentric triaxial copolymeric initiator of about 90 percent by mole trimethylene carbonate and about 10 percent by mole ε-caprolactone with a mixture of about 95 percent by mole ε-caprolactone and about 5 percent by mole glycolide. 
     
     
         3 . A polymeric drug carrier, suture-specific coating as set forth in  claim 2  wherein the copolyester has molecularly dispersed therein greater than about 2 weight percent of an antimicrobial agent comprising triclosan. 
     
     
         4 . A polymeric drug carrier, suture-specific coating as set forth in  claim 2  wherein the copolyester has molecularly dispersed therein up to about 10 weight percent of an anti-neoplastic agent selected from leflunamide and paclitaxel. 
     
     
         5 . A polymeric drug carrier, suture-specific coating as set forth in  claim 2  wherein the coating is applied to an absorbable, braided multifilament suture comprising a high-glycolide, segmented, polyaxial copolyester. 
     
     
         6 . A polymeric drug carrier, suture-specific coating as set forth in  claim 1  wherein the copolyester is made by end-grafting an amorphous, monocentric triaxial copolymeric initiator of about 85 percent by mole trimethylene carbonate and about 15 percent by mole ε-caprolactone with a mixture of about 95 percent by mole ε-caprolactone and about 5 percent by mole glycolide, the copolyester having molecularly dispersed therein greater than about 2 weight percent of an antimicrobial agent comprising triclosan, wherein the coating is applied to an absorbable, compliant monofilament suture comprising a high-glycolide segmented linear copolyester. 
     
     
         7 . A polymeric drug carrier, suture-specific coating as set forth in  claim 1  wherein the copolyester is made by the ring-opening polymerization of a mixture of about 95 percent by mole ε-caprolactone and about 5 percent by mole glycolide in the presence of an initiator and a catalyst comprising stannous octanoate, the copolyester having molecularly dispersed therein an antimicrobial agent comprising triclosan. 
     
     
         8 . A polymeric drug carrier, suture-specific coating as set forth in  claim 7  wherein the initiator comprises triethanolamine, wherein the triclosan is present at greater than about 2 percent by weight, and wherein the coating is applied to an absorbable, braided multifilament suture comprising a high lactide, segmented, linear copolyester. 
     
     
         9 . A polymeric drug carrier, suture-specific coating as set forth in  claim 7  wherein the initiator comprises triethanolamine, wherein the triclosan is present at greater than about 2 percent by weight, and wherein the coating is applied to an absorbable monofilament suture comprising a high lactide, segmented, polyaxial copolyester. 
     
     
         10 . A polymeric drug carrier, suture-specific coating as set forth in  claim 1  wherein the copolyester is made by end-grafting an amorphous monocentric, triaxial copolymeric initiator, prepared by the ring-opening polymerization of about 90 percent by mole of trimethylene carbonate and about 10 percent by mole of ε-caprolactone in the presence of trimethylolpropane and stannous octanoate, with a mixture of about 95 percent by mole of ε-caprolactone and about 5 percent by mole of l-lactide, the resulting copolyester having molecularly dispersed therein greater than about 2 weight percent of an antimicrobial agent comprising triclosan, wherein the coating is applied to a multifilament braided silk suture. 
     
     
         11 . A polymeric drug carrier, suture-specific coating as set forth in  claim 10  wherein the silk suture comprises a dyed silk suture. 
     
     
         12 . A polymeric drug carrier, suture-specific coating as set forth in  claim 1  wherein the copolyester is made by the ring-opening polymerization of ε-caprolactone in the presence of an initiator comprising trimethylolpropane and a catalyst comprising stannous octanoate, the copolyester having molecularly dispersed therein an antimicrobial agent comprising triclosan. 
     
     
         13 . A polymeric drug carrier, suture-specific coating as set forth in  claim 12  wherein the triclosan is present at greater than about 2 percent by weight and wherein the coating is applied to a non-absorbable monofilament suture comprising at least one polymer selected from the group consisting of a linear aliphatic polyamide, a polyalkylene terephthalate-polyether segmented copolymer, and polypropylene. 
     
     
         14 . A polymeric drug carrier, suture-specific coating as set forth in  claim 12  wherein the triclosan is present at greater than about 2 percent by weight and wherein the coating is applied to a non-absorbable multifilament braided suture comprising at least one polymer selected from the group consisting of a linear aliphatic polyamide, a linear aromatic polyester, polypropylene, and ultrahigh molecular weight polyethylene. 
     
     
         15 . A polymeric drug carrier, suture-specific coating as set forth in  claim 1  applied to a suture, sterilized, and packaged for use in tissue repair requiring reliable ligation over a period ranging from one to eight weeks.