Bio-degradable/ absorbable polymer having reduced metal catalyst content, and process for production thereof

Abstract

The present invention provides a safe biodegradable and bioabsorbable polymer having an extremely low metal catalyst content, while retaining the properties desired for a medical implant or the like; and a process for producing the same. The present invention further provides a method for reducing the content of a metal catalyst in a biodegradable and absorbable polymer that can be applied on an industrial scale. A method for producing a biodegradable and bioabsorbable polymer having a metal catalyst content of less than 1 ppm in terms of a metal comprising the steps of (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 40/60 to 60/40 in the presence of the metal catalyst to produce a copolymer; and (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 25/75 to 45/55 at less than 40° C., and drying the copolymer. 13. A method for producing a biodegradable and bioabsorbable polymer having a metal catalyst content of less than 1 ppm in terms of a metal comprising the steps of (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 65/35 to 85/15 in the presence of the metal catalyst to produce a copolymer; and (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 45/55 to 55/45 at less than 40° C., and drying the copolymer.

1 . A biodegradable and bioabsorbable polymer comprising a copolymer of lactide and ε-caprolactone, the polymer having a metal catalyst content of less than 1 ppm in terms of a metal. 
   
   
       2 . The biodegradable and bioabsorbable polymer according to  claim 1 , wherein the polymer comprises a copolymer of lactide and ε-caprolactone at a molar ratio ranging from 40/60 to 60/40, or a copolymer of lactide and ε-caprolactone at a molar ratio ranging from 65/35 to 85/15; and the polymer has a metal catalyst content of less than 1 ppm in terms of a metal. 
   
   
       3 . A medical implant comprising the biodegradable and bioabsorbable polymer according to  claim 1 . 
   
   
       4 . A method for producing a biodegradable and bioabsorbable polymer having a metal catalyst content of less than 1 ppm in terms of a metal comprising the steps of:
 (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 40/60 to 60/40 in the presence of the metal catalyst to produce a copolymer; and   (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 25/75 to 45/55 at less than 40° C., and drying the copolymer.   
   
   
       5 . The method according to  claim 4 , wherein a lactic acid forming the lactide in Step (1) is L-form, D-form, or DL-form. 
   
   
       6 . The method according to  claim 4 , wherein the temperature of the mixed solvent during the washing in Step (2) is about 15° C. to about 30° C. 
   
   
       7 . The method according to  claim 4 , wherein the mixed solvent is exchanged five times or more, and the washing time is a total of 48 hours or more in Step (2). 
   
   
       8 . The method according to  claim 4 , wherein the metal catalyst is at least one member selected from the group consisting of tin octylate (II), tin 2-ethylhexanoate, triphenyltin acetate, tin oxide, dibutyltin oxide, tin oxalate, tin chloride, and dibutyltin dilaurate. 
   
   
       9 . The method according to  claim 4 , wherein the copolymer after washing is vacuum-dried at about 20° C. to about 35° C. for about 10 to about 30 hours, and then vacuum-dried at about 35° C. to about 50° C. for about 40 to about 100 hours. 
   
   
       10 . A method of reducing the content of a metal catalyst in a biodegradable and bioabsorbable polymer to less than 1 ppm in terms of a metal comprising the steps of:
 (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 40/60 to 60/40 in the presence of the metal catalyst to produce a copolymer; and   (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 25/75 to 45/55 at less than 40° C., and drying the copolymer.   
   
   
       11 . A method for producing a medical implant comprising the steps of:
 (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 40/60 to 60/40 in the presence of a metal catalyst to produce a copolymer;   (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 25/75 to 45/55 at less than 40° C., and drying the copolymer, so that the metal catalyst content becomes less than 1 ppm in terms of a metal; and   (3) forming the copolymer obtained in Step (2) into the medical implant.   
   
   
       12 . The method according to  claim 11 , wherein the medical implant is selected from the group consisting of sutures, bone-joining materials, fracture fixation materials, tissue supplementation materials, tissue reinforcing materials, tissue covering materials, tissue regenerating base materials, tissue prosthetic materials, anti-adhesive materials, artificial blood vessels, artificial valves, stents, clips, fiber cloths, hemostatic materials, adhesives, and coating agents. 
   
   
       13 . A method for producing a biodegradable and bioabsorbable polymer having a metal catalyst content of less than 1 ppm in terms of a metal comprising the steps of:
 (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 65/35 to 85/15 in the presence of the metal catalyst to produce a copolymer; and   (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 45/55 to 55/45 at less than 40° C., and drying the copolymer.   
   
   
       14 . The method according to  claim 13 , wherein a lactic acid forming the lactide in Step (1) is L-form, D-form, or DL-form. 
   
   
       15 . The method according to  claim 13 , wherein the temperature of the mixed solvent during washing in Step (2) is about 15° C. to about 30° C. 
   
   
       16 . The method according to  claim 13 , wherein the mixed solvent is exchanged four times or more, and the washing time is a total of 30 hours or more in Step (2). 
   
   
       17 . The method according to  claim 13 , wherein the metal catalyst is at least one member selected from the group consisting of tin octylate (II), tin 2-ethylhexanoate, triphenyltin acetate, tin oxide, dibutyltin oxide, tin oxalate, tin chloride, and dibutyltin dilaurate. 
   
   
       18 . The method according to  claim 13 , wherein the copolymer after washing is vacuum-dried at about 20° C. to about 35° C. for about 10 to about 30 hours, and then vacuum-dried at about 35° C. to about 50° C. for about 40 to about 100 hours. 
   
   
       19 . A method of reducing the content of a metal catalyst in a biodegradable and bioabsorbable polymer to less than 1 ppm in terms of a metal comprising the steps of:
 (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 65/35 to 85/15 in the presence of the metal catalyst to produce a copolymer; and   (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 45/55 to 55/45 at less than 40° C., and drying the copolymer.   
   
   
       20 . A method for producing a medical implant comprising the steps of:
 (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 65/35 to 85/15 in the presence of a metal catalyst to produce a copolymer;   (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 45/55 to 55/45 at less than 40° C., and drying the copolymer, so that the metal catalyst content becomes less than 1 ppm in terms of a metal; and   (3) forming the copolymer obtained in Step (2) into the medical implant.   
   
   
       21 . The method according to  claim 20 , wherein the medical implant is selected form the group consisting of sutures, bone-joining materials, fracture fixation materials, tissue supplementation materials, tissue reinforcing materials, tissue covering materials, tissue regenerating base materials, tissue prosthetic materials, anti-adhesive materials, artificial blood vessels, artificial valves, stents, clips, fiber cloths, hemostatic materials, adhesives, and coating agents.