Advanced Processing of Absorbable Poly(p-dioxanone) Containing High Level of p-Dioxanone Monomer

Abstract

The present invention is directed methods of making absorbable poly(p-dioxanone) pellets by melt polymerization of p-dioxanone conducted in a single reactor with a temperature regulator by charging a melt reactor with a mixture of p-dioxanone (PDO) monomer, initiator, catalyst, and optionally a dye; melt polymerizing the mixture in the melt reactor with sufficient agitation of the mixture to allow complete mixing of the monomer and for sufficient time to form a PDO polymer product having an unreacted PDO monomer content of at least 65 mole percent; placing the PDO polymer product under a vacuum to remove at least portion of unreacted PDO; discharging the PDO polymer product from the melt reactor directly into an in-line, underwater pelletizer to produce undried PDO pellets, collecting the undried PDO pellets, and storing the collected PDO pellets in the freezer or a vacuum chamber prior to drying.

I/We claim: 
     
         1 . A polymeric filament extruded from a PDO pellet made in accordance with the method of making absorbable poly(p-dioxanone) pellets by melt polymerization of p-dioxanone conducted in a single reactor with a temperature regulator, and comprising the steps of:
 i. charging a melt reactor with a mixture of p-dioxanone (PDO) monomer, initiator, catalyst, and optionally a dye;   ii. melt polymerizing the mixture at a reaction temperature of between 95° C. and 145° C. in the melt reactor with sufficient agitation of the mixture to allow complete mixing of the monomer and for sufficient time to form a PDO polymer product of at least 65 mole percent having an unreacted PDO monomer content;   iii. placing the PDO polymer product under a vacuum for about 60 to 180 minutes to remove at least portion of unreacted PDO, as measured by monomer content;   iv. discharging the PDO polymer product from the melt reactor directly into an in-line, underwater pelletizer to produce undried PDO pellets,   v. collecting the undried PDO pellets, and   vi. storing the collected PDO pellets in the freezer or a vacuum chamber.   
     
     
         2 . A polymeric filament made in accordance with the method of  claim 1 , wherein the melt polymerization of PDO monomer is conducted in a single reactor in the presence of a monofunctional initiator at an initiator concentration of between 500:1 to 2,000:1 (mole of monomer: mole of initiator), and in the presence of a catalyst in the total amount of 30,000:1 to 300,000:1 (moles of monomer: moles of catalyst), for total reaction time of between 4 hours and 16 hours. 
     
     
         3 . A polymeric filament made in accordance with the method of  claim 2 , wherein the monofunctional initiator is dodecanol. 
     
     
         4 . A polymeric filament made in accordance with the method of  claim 2 , wherein the catalyst is stannous octoate. 
     
     
         5 . A polymeric filament made in accordance with the method of  claim 2 , wherein the dye is D&C Violet Number 2 in a dye concentration of between 0.01 and 0.2 weight percentage. 
     
     
         6 . A polymeric filament made in accordance with the method of  claim 1 , wherein the unreacted PDO monomer content after step (iii) is between about 15 mole percent to about 35 mole percent and wherein pelletization is conducted by the underwater pelletizer having a pump and a cutter under following conditions:
 a. Setting the melt reactor to an operating temperature of from 95° C. to 130° C.;   b. Initially setting the melt rector agitator at a rotational speed of between 2 RPM to 6 RPM or from about 20-40% of the rotational speed for step (ii);   c. Initially setting the pump speed in the pelletizer at about 5 RPM to about 7 RPM, and gradually increasing the pump speed to the range between 10 RPM and 15 RPM;   d. Setting the pelletizer to a die temperature of about 100° C. to 140° C.;   e. Setting the cutter to a rotational speed of between about 2,000 and 3,600 RPM.   
     
     
         7 . A polymeric filament made in accordance with the method of  claim 1  further comprising the step of drying the poly(p-dioxanone) pellets. 
     
     
         8 . A polymeric filament made in accordance with the method of  claim 7  wherein the poly(p-dioxanone) pellets are dried using a fluidized bed drying apparatus. 
     
     
         9 . A polymeric filament made in accordance with the method of  claim 7 , wherein the drying is conducted using tumble dryers, equipped with vacuum and/or heating capabilities, including the steps of:
 a. Transferring undried poly(p-dioxanone) pellets having an unreacted p-dioxanone monomer content of between about 15 mole percent to about 35 mole percent into a tumble drier,   b. applying a vacuum in the tumble drier at room temperature and reducing the moisture level in poly(p-dioxanone) pellets to less than 100 parts per million, as measured by a moisture analyzer;   c. setting the drier temperature to a starting drying temperature of about 55° C. and maintaining the heat and vacuum for about two to six hours;   d. setting the drier temperature to an intermediate drying temperature of about 75° C. and maintaining the heat and vacuum for about two to six hours;   e. setting the drier temperature to a final drying temperature from about 85° C. to 95° C. and maintaining the heat and vacuum for about 16 to 32 hours; and   f. collecting the dried poly(p-dioxanone) pellets.   
     
     
         10 . The polymeric filament made in accordance with the method of  claim 9 , wherein the dried poly(p-dioxanone) pellets contain less than 4 mole % of unreacted PDO monomer at the end of drying process. 
     
     
         11 . The polymeric filament made in accordance with the method of  claim 9 , wherein the dried poly(p-dioxanone) pellets have an inherent viscosity (IV) as measured in hexafluoroisopropanol at 25° C. and at a concentration of 0.10 g/dL of greater than 1.2 dl/g. 
     
     
         12 . The polymeric filament made in accordance with the method of  claim 9 , wherein the dried poly(p-dioxanone) pellets have a weight average molecular weight (Mw) greater than 50,000 Daltons, as measured by gel permeation chromatography. 
     
     
         13 . The polymeric filament made in accordance with the method of  claim 9 , wherein the dried poly(p-dioxanone) pellets have a crystallinity level greater than 45% as measured by Wide Angle X-ray Diffraction (WAXD) after being subjected to a heat treatment between about 60° C. and 90° C. for at least six hours.